Skip to main content
×
×
Home
  • Print publication year: 2014
  • Online publication date: May 2014

Section 5 - Determinants of regeneration in the injured nervous system

Recommend this book

Email your librarian or administrator to recommend adding this book to your organisation's collection.

Textbook of Neural Repair and Rehabilitation
  • Online ISBN: 9780511995583
  • Book DOI: https://doi.org/10.1017/CBO9780511995583
Please enter your name
Please enter a valid email address
Who would you like to send this to *
×

References

1. CebriàF. Regenerating the central nervous system: how easy for planarians! Dev Genes Evol 2007; 217: 733–48.
2. AgataK, SoejimaY, KatoK, et al. Structure of the planarian central nervous system (CNS) revealed by neuronal cell markers. Zoolog Sci 1998; 15: 433–40.
3. GentileL, CebriàF, BartschererK. The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration. Dis Model Mech 2011; 4: 12–19.
4. UmesonoY, AgataK. Evolution and regeneration of the planarian central nervous system. Dev Growth Differ 2009; 51: 185–95.
5. KobayashiC, SaitoY, OgawaK, et al. Wnt signaling is required for antero-posterior patterning of the planarian brain. Dev Biol; 306: 714–24.
6. WhiteJG, SouthgateE, ThomsonJN, et al. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 1986; 314: 1–340.
7. YanikMF, CinarH, CinarHN, et al. Neurosurgery: functional regeneration after laser axotomy. Nature 2004; 432: 822.
8. HammarlundM, NixP, HauthL, et al. Axon regeneration requires a conserved MAP kinase pathway. Science 2009; 323: 802–6.
9. Ghosh-RoyA, WuZ, GoncharovA, et al. Calcium and cyclic AMP romote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J Neurosci 2010; 30: 3175–83.
10. NeumannB, NguyenKCQ, HallDH, et al. Axonal regeneration proceeds through specific axonal fusion in transected C. elegans neurons. Dev Dyn 2011; 240: 1365–72.
11. BittnerGD. Long-term survival of anucleate axons and its implications for nerve regeneration. Trends Neurosci 1991; 14: 188–93.
12. FrankE, JansenJK, RinvikE. A multisomatic axon in the central nervous system of the leech. J Comp Neurol 1975; 159: 1–13.
13. HoyRR, BittnerGD, KennedyD. Regeneration in crustacean motoneurons: evidence for axonal fusion. Science 1967; 156: 251–2.
14. CohenAH, MacklerSA, SelzerME. Behavioral recovery following spinal transection: functional regeneration in the lamprey CNS. Trends Neurosci 1988; 11: 227–31.
15. RovainenCM. Neurobiology of lampreys. Physiol Rev 1979; 59: 1007–77.
16. BullockTH, MooreJK, FieldsRD. Evolution of myelin sheaths: both lamprey and hagfish lack myelin. Neurosci Lett 1984; 48: 145–8.
17. SelzerME. Variability in maps of identified neurons in the sea lamprey spinal cord examined by a wholemount technique. Brain Res 1979; 163: 181–93.
18. YinHS, SelzerME. Axonal regeneration in lamprey spinal cord. J Neurosci 1983; 3: 1135–44.
19. SelzerME. Mechanisms of functional recovery and regeneration after spinal cord transection in larval sea lamprey. J Physiol (Lond) 1978; 277: 395–408.
20. YinHS, MacklerSA, SelzerME. Directional specificity in the regeneration of lamprey spinal axons. Science 1984; 224: 894–6.
21. MacklerSA, SelzerME. Specificity of synaptic regeneration in the spinal cord of the larval sea lamprey. J Physiol (Lond) 1987; 388: 183–98.
22. ShifmanMI, SelzerME. Differential expression of Class 3 and 4 semaphorins and netrin in the lamprey spinal cord during regeneration. J Comp Neurol 2007; 501: 631–46.
23. ShifmanMI, YumulRE, LaramoreC, et al. Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey. Exp Neurol 2009; 217: 242–51.
24. DavisGR, McClellanAD. Extent and time course of restoration of descending brainstem projections in spinal cord-transected lamprey. J Comp Neurol 1994; 344: 65–82.
25. JacobsAJ, SwainGP, SnedekerJA, et al. Recovery of neurofilament expression selectively in regenerating reticulospinal neurons. J Neurosci 1997; 17: 5206–20.
26. ShifmanMI, SelzerME. Semaphorins and their receptors in lamprey CNS: cloning, phylogenetic analysis and developmental changes during metamorphosisJ Comp Neurol 2006; 497: 115–32.
27. ShifmanMI, SelzerME. Expression of netrin receptor UNC-5 in lamprey brain; modulation by spinal cord transection. Neurorehabil Neural Repair 2000; 14: 49–58.
28. ShifmanMI, ZhangG, SelzerME. Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys. J Comp Neurol 2008; 510: 269–82.
29. BernsteinJJ, BernsteinME. Effect of glial-ependymal scar and Teflon arrest on the regenerative capacity of goldfish spinal cord. Exp Neurol 1967; 19: 25–32.
30. CoggeshallRE, YoungbloodCS. Recovery from spinal transection in fish: regrowth of axons past the transection. Neurosci Lett 1983; 38: 227–31.
31. TakedaA, GorisRC, FunakoshiK. Regeneration of descending projections to the spinal motor neurons after spinal hemisection in the goldfish. Brain Res 2007; 1155: 17–23.
32. BernsteinJJ, GelderdJB. Synaptic reorganization following regeneration of goldfish spinal cord. Exp Neurol 1973; 41: 402–10.
33. ZottoliSJ, FreemerMM. Recovery of C-starts, equilibrium and targeted feeding after whole spinal cord crush in the adult goldfish Carassius auratus. J Exp Biol 2003; 206: 3015–29.
34. ZottoliSJ, BentleyAP, FeinerDG, et al. Spinal cord regeneration in adult goldfish: implications for functional recovery in vertebrates. Prog Brain Res 1994; 103: 219–28.
35. BeckerCG, BeckerT. Adult zebrafish as a model for successful central nervous system regeneration. Restor Neurol Neurosci 2008; 26: 71–80.
36. BhattDH, PatzelovaH, McLeanDL, et al. Functional regeneration in the larval zebrafish spinal cord. In BeckerCG, BeckerT, eds. Model Organisms in Spinal Cord Regeneration. KGaA:Wiley-VCH Verlag GmbH & Co., 2007; 263–88.
37. BeckerT, WullimannMF, BeckerCG, et al. Axonal regrowth after spinal cord transection in adult zebrafish. J Comp Neurol 1997; 377: 577–95.
38. BeckerT, BeckerCG. Regenerating descending axons preferentially reroute to the gray matter in the presence of a general macrophage/microglial reaction caudal to a spinal transection in adult zebrafish. J Comp Neurol 2001; 433: 131–47.
39. BeckerT, LieberothBC, BeckerCG, et al. Differences in the regenerative response of neuronal cell populations and indications for plasticity in intraspinal neurons after spinal cord transection in adult zebrafish. Mol Cell Neurosci 2005; 30: 265–78.
40. BeckerCG, LieberothBC, MorelliniF, et al. L1.1 is involved in spinal cord regeneration in adult zebrafish. J Neurosci 2004; 24: 7837–42.
41. BeckerT, BernhardtRR, ReinhardE, et al. Readiness of zebrafish brain neurons to regenerate a spinal axon correlates with differential expression of specific cell recognition molecules. J Neurosci 1998; 18: 5789–803.
42. DunlopSA. Functional aspects of optical nerve regeneration in non-mammalian vertebrates. In BeckerCG, BeckerT, eds. Model Organisms in Spinal Cord Regeneration. KGaA: Wiley-VCH Verlag GmbH&Co; 2007; 323–54.
43. SandvigA, BerryM, BarrettLB, et al. Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: Expression, receptor signaling, and correlation with axon regeneration. Glia 2004; 46: 225–51.
44. FawcettJW, AsherRA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49: 377–91.
45. FawcettJW. Overcoming inhibition in the damaged spinal cord. J Neurotrauma 2006; 23: 371–83.
46. GigerRJ, HollisER, TuszynskiMH. Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol 2010; 2: a001867.
47. WannerM, LangDM, BandtlowCE, et al. Reevaluation of the growth-permissive substrate properties of goldfish optic nerve myelin and myelin proteins. J Neurosci 1995; 15: 7500–8.
48. BastmeyerM, BeckmannM, SchwabM, et al. Growth of regenerating goldfish axons is inhibited by rat oligodendrocytes and CNS myelin but not by goldfish optic nerve tract oligodendrocytelike cells and fish CNS myelin. J Neurosci 1991; 11: 626–40.
49. BormannP, ZumstegVM, RothLW, et al. Target contact regulates GAP-43 and alpha-tubulin mRNA levels in regenerating retinal ganglion cells. J Neurosci Res 1998; 52: 405–19.
50. MatsukawaT, AraiK, KoriyamaY, et al. Axonal regeneration of fish optic nerve after injury. Biol Pharm Bull 2004; 27: 445–51.
51. BeckerCG, MeyerRL, BeckerT. Gradients of ephrin-A2 and ephrin-A5b mRNA during retinotopic regeneration of the optic projection in adult zebrafish. J Comp Neurol 2000; 427: 469–83.
52. MatsunagaE, NakamuraH, ChedotalA. Repulsive guidance molecule plays multiple roles in neuronal differentiation and axon guidance. J Neurosci 2006; 26: 6082–8.
53. DavisBM, AyersJL, KoranL, et al. Time course of salamander spinal cord regeneration and recovery of swimming: HRP retrograde pathway tracing and kinematic analysis. Exp Neurol 1990; 108: 198–213.
54. ChevallierS, LandryM, NagyF, et al. Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles waltlii. Eur J Neurosci 2004; 20: 1995–2007.
55. DavisBM, DuffyMT, SimpsonSB Jr. Bulbospinal and intraspinal connections in normal and regenerated salamander spinal cord. Exp Neurol 1989; 103: 41–51.
56. ZukorKA, KentDT, OdelbergSJ. Meningeal cells and glia establish a permissive environment for axon regeneration after spinal cord injury in newts. Neural Dev 2011; 6: 1.
57. BleschA, TuszynskiMH. Spinal cord injury: plasticity, regeneration and the challenge of translational drug development. Trends Neurosci 2009; 32: 41–7.
58. SimsRT. Transection of the spinal cord in developing Xenopus laevis. J Embryol Exp Morphol 1962; 10: 115–26.
59. ForehandCJ, FarelPB. Anatomical and behavioral recovery from the effects of spinal cord transection: dependence on metamorphosis in anuran larvae. J Neurosci 1982; 2: 654–52.
60. BeattieMS, BresnahanJC, LopateG. Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs. J Neurobiol 1990; 21: 1108–22.
61. GibbsKM, ChitturSV, SzaroBG. Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis. Eur J Neurosci 2011; 33: 9–25.
62. GibbsKM, SzaroBG. Regeneration of descending projections in Xenopus laevis tadpole spinal cord demonstrated by retrograde double labeling. Brain Res 2006; 1088: 68–72.
63. PiattJ, PiattM. Transection of the spinal cord in the adult frog. Anat Rec 1958; 131: 81–95.
64. MladinicM, MullerKJ, NichollsJG. Central nervous system regeneration: from leech to opossum. J Physiol 2009; 587: 2775–82.
65. SmithJ, MorganJR, ZottoliSJ, et al. Regeneration in the era of functional genomics and gene network analysis. Biol Bull 2011; 221: 18–34.
66. Marsh-ArmstrongN, CaiL, BrownDD. Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis. Proc Natl Acad Sci U S A 2004; 101: 165–70.
67. LangDM, RubinBP, SchwabME, et al. CNS myelin and oligodendrocytes of the Xenopus spinal cord–but not optic nerve–are nonpermissive for axon growth. J Neurosci 1995; 15: 99–109.
68. VargaZM, BandtlowCE, ErulkarSD, et al. The critical period for repair of CNS of neonatal opossum (Monodelphis domestica) in culture: correlation with development of glial cells, myelin and growth-inhibitory molecules. Eur J Neurosci 1995; 7: 2119–29.
69. FitchMT, SilverJ. CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp Neurol 2008; 209: 294–301.
70. LurieDI, PijakDS, SelzerME. Structure of reticulospinal axon growth cones and their cellular environment during regeneration in the lamprey spinal cord. J Comp Neurol 1994; 344: 559–80.
71. ZornerB, SchwabME. Anti-Nogo on the go: from animal models to a clinical trial. Ann N Y Acad Sci 2010; 1198: E22–34.
72. BartusK, JamesND, BoschKD, et al. Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity. Exp Neurol 2012; 235: 5–17.
73. ZhengB, HoC, LiS, et al. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 2003; 38: 213–24.
74. StewardO, SharpK, YeeKM, et al. A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice. Exp Neurol 2008; 209: 446–68.
75. LeeJK, GeoffroyCG, ChanAF, et al. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 2010; 66: 663–70.
76. GargioliC, SlackJM. Cell lineage tracing during Xenopus tail regeneration. Development 2004; 131: 2669–79.
77. BenraissA, ArsantoJP, CoulonJ, et al. Neurogenesis during caudal spinal cord regeneration in adult newts. Dev Genes Evol 1999; 209: 363–9.
78. EcheverriK, TanakaEM. Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science 2002; 298: 1993–6.
79. Sanchez AlvaradoA, TsonisPA. Bridging the regeneration gap: genetic insights from diverse animal models. Nat Rev Genet 2006; 7: 873–84.
80. TsengAS, LevinM. Tail regeneration in Xenopus laevis as a model for understanding tissue repair. J Dent Res 2008; 87: 806–16.
81. TanakaEM, FerrettiP. Considering the evolution of regeneration in the central nervous system. Nat Rev Neurosci 2009; 10: 713–23.
82. Del Rio-TsonisK, TsonisPA. Eye regeneration at the molecular age. Dev Dyn 2003; 226: 211–24.
83. YoshiiC, UedaY, OkamotoM, et al. Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: transdifferentiation of retinal pigmented epithelium regenerates the neural retina. Dev Biol 2007; 303: 45–56.
84. VergaraMN, Del Rio-TsonisK. Retinal regeneration in the Xenopus laevis tadpole: a new model system. Mol Vis 2009; 15: 1000–13.
85. KarlMO, RehTA. Regenerative medicine for retinal diseases: activating endogenous repair mechanisms. Trends Mol Med 2010; 16: 193–202.
86. CheonEW, KanekoY, SaitoT. Regeneration of the newt retina: order of appearance of photoreceptors and ganglion cells. J Comp Neurol 1998; 396: 267–74.
87. SakaguchiDS, JanickLM, RehTA. Basic fibroblast growth factor (FGF-2) induced transdifferentiation of retinal pigment epithelium: generation of retinal neurons and glia. Dev Dyn 1997; 209: 387–98.
88. SperryRW. Optic nerve regeneration with return of vision in anurans. J Neurophysiol 1944; 7: 57–69.
89. StensaasLJ, FeringaER. Axon regeneration across the site of injury in the optic nerve of the newt Triturus pyrrhogaster. Cell Tissue Res 1977; 179: 501–16.
90. FujisawaH. Retinotopic analysis of fiber pathways in the regenerating retinotectal system of the adult newt cynops Pyrrhogaster. Brain Res 1981; 206: 27–37.
91. FawcettJW, GazeRM. The organization of regenerating axons in the Xenopus optic nerve. Brain Res 1981; 229: 487–90.
92. OkamotoM, OhsawaH, HayashiT, et al. Regeneration of retinotectal projections after optic tectum removal in adult newts. Mol Vis 2007; 13: 2112–8.
93. SperryRW. Visuomotor coordination in the newt (Triturus viridescens) after regeneration of the optic nerve. J Comp Neurol 1943; 79: 33–55.
94. BachH, ArangoV, FeldheimD, et al. Fiber order of the normal and regenerated optic tract of the frog (Rana pipiens). J Comp Neurol 2004; 477: 43–54.
95. FeldheimDA, O’LearyDD. Visual map development: bidirectional signaling, bifunctional guidance molecules, and competition. Cold Spring Harb Perspect Biol 2010; 2: a001768.
96. RuthazerES, ClineHT. Insights into activity-dependent map formation from the retinotectal system: a middle-of-the-brain perspective. J Neurobiol 2004; 59: 134–46.
97. RehermannMI, MarichalN, RussoRE, et al. Neural reconnection in the transected spinal cord of the freshwater turtle Trachemys dorbignyi. J Comp Neurol 2009; 515: 197–214.
98. RehermannMI, SantinaqueFF, Lopez-CarroB, et al. Cell proliferation and cytoarchitectural remodeling during spinal cord reconnection in the fresh-water turtle Trachemys dorbignyi. Cell Tissue Res 2011; 344: 415–33.
99. FernandezA, RadmilovichM, Trujillo-CenozO. Neurogenesis and gliogenesis in the spinal cord of turtles. J Comp Neurol 2002; 453: 131–44.
100. BeazleyLD, SheardPW, TennantM, et al. Optic nerve regenerates but does not restore topographic projections in the lizard Ctenophorus ornatus. J Comp Neurol 1997; 377: 105–20.
101. DunlopSA, TeeLB, StirlingRV, et al. Failure to restore vision after optic nerve regeneration in reptiles: interspecies variation in response to axotomy. J Comp Neurol 2004; 478: 292–305.
102. BeazleyLD, RodgerJ, ChenP, et al. Training on a visual task improves the outcome of optic nerve regeneration. J Neurotrauma 2003; 20: 1263–70.
103. FongAJ, RoyRR, IchiyamaRM, et al. Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face. Prog Brain Res 2009; 175: 393–418.

References

1. Ramón y CajalS. Degeneration and Regeneration of the Nervous System. New York, NY: Hafner, 1928.
2. DavidS, AguayoAJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 1981; 214: 931–3.
3. BerryM. Post-injury myelin-breakdown products inhibit axonal growth: an hypothesis to explain the failure of axonal regeneration in the mammalian central nervous system. Bibl Anat 1982; 23: 1–11.
4. SchwabME, CaroniP. Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci 1988; 8: 2381–93.
5. CaroniP, SchwabME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106: 1281–8.
6. CaroniP, SchwabME. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1988; 1: 85–96.
7. SchnellL, SchwabME. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 1990; 343: 269–72.
8. BregmanBS, Kunkel-BagdenE, SchnellL, et al. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 1995; 378: 498–501.
9. ThallmairM, MetzGA, Z’GraggenWJ, et al. Neurite growth inhibitors restrict plasticity and functional recovery following corticospinal tract lesions. Nat Neurosci 1998; 1: 124–31.
10. von MeyenburgJ, BrosamleC, MetzGA, et al. Regeneration and sprouting of chronically injured corticospinal tract fibers in adult rats promoted by NT-3 and the mAb IN-1, which neutralizes myelin-associated neurite growth inhibitors. Exp Neurol 1998; 154: 583–94.
11. Z’GraggenWJ, MetzGA, KartjeGL, et al. Functional recovery and enhanced corticofugal plasticity after unilateral pyramidal tract lesion and blockade of myelin-associated neurite growth inhibitors in adult rats. J Neurosci 1998; 18: 4744–57.
12. RaineteauO, Z’GraggenWJ, ThallmairM, et al. Sprouting and regeneration after pyramidotomy and blockade of the myelin-associated neurite growth inhibitors NI 35/250 in adult rats. Eur J Neurosci 1999; 11: 1486–90.
13. MerklerD, MetzGA, RaineteauO, et al. Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A. J Neurosci 2001; 21: 3665–73.
14. RaineteauO, FouadK, NothP, et al. Functional switch between motor tracts in the presence of the mAb IN-1 in the adult rat. Proc Natl Acad Sci U S A 2001; 98: 6929–34.
15. FouadK, KlusmanI, SchwabME. Regenerating corticospinal fibers in the marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1. Eur J Neurosci 2004; 20: 2479–82.
16. BrosamleC, HuberAB, FiedlerM, et al. Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci 2000; 20: 8061–8.
17. BandtlowC, SchiweckW, TaiHH, et al. The Escherichia coli-derived Fab fragment of the IgM/kappa antibody IN- 1 recognizes and neutralizes myelin-associated inhibitors of neurite growth. Eur J Biochem 1996; 241: 468–75.
18. SpillmannAA, BandtlowCE, LottspeichF, et al. Identification and characterization of a bovine neurite growth inhibitor (bNI-220). J Biol Chem 1998; 273: 19283–93.
19. ChenMS, HuberAB, van der HaarME, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434–9.
20. GrandPreT, NakamuraF, VartanianT, et al. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 2000; 403: 439–44.
21. PrinjhaR, MooreSE, VinsonM, et al. Inhibitor of neurite outgrowth in humans. Nature 2000; 403: 383–4.
22. FournierAE, GrandPreT, StrittmatterSM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409: 341–6.
23. OertleT, van der HaarME, BandtlowCE, et al. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci 2003; 23: 5393–406.
24. HuF, StrittmatterSM. The N-terminal domain of Nogo-A inhibits cell adhesion and axonal outgrowth by an integrin-specific mechanism. J Neurosci 2008; 28: 1262–9.
25. McKerracherL, DavidS, JacksonDL, et al. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 1994; 13: 805–11.
26. MukhopadhyayG, DohertyP, WalshFS, et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994; 13: 757–67.
27. CaiD, QiuJ, CaoZ, et al. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 2001; 21: 4731–9.
28. WangKC, KoprivicaV, KimJA, et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 2002; 417: 941–4.
29. LiuBP, FournierA, GrandPreT, et al. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science 2002; 297: 1190–3.
30. DomeniconiM, CaoZ, SpencerT, et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 2002; 35: 283–90.
31. KimJE, LiuBP, ParkJH, et al. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron 2004; 44: 439–51.
32. ZhengB, AtwalJ, HoC, et al. Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc Natl Acad Sci U S A 2005; 102: 1205–10.
33. ChivatakarnO, KanekoS, HeZ, et al. The Nogo-66 receptor NgR1 is required only for the acute growth cone-collapsing but not the chronic growth-inhibitory actions of myelin inhibitors. J Neurosci 2007; 27: 7117–24.
34. AtwalJK, Pinkston-GosseJ, SykenJ, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 2008; 322: 967–70.
35. WangKC, KimJA, SivasankaranR, et al. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 2002; 420: 74–8.
36. ParkJB, YiuG, KanekoS, et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 2005; 45: 345–51.
37. ShaoZ, BrowningJL, LeeX, et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005; 45: 353–9.
38. MiS, LeeX, ShaoZ, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004; 7: 221–8.
39. VenkateshK, ChivatakarnO, LeeH, et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 2005; 25: 808–22.
40. NiederostB, OertleT, FritscheJ, et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 2002; 22: 10368–76.
41. YamashitaT, HiguchiH, TohyamaM. The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol 2002; 157: 565–70.
42. LiebscherT, SchnellL, SchnellD, et al. Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol 2005; 58: 706–19.
43. GrandPreT, LiS, StrittmatterSM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 2002; 417: 547–51.
44. LiS, LiuBP, BudelS, et al. Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J Neurosci 2004; 24: 10511–20.
45. FreundP, SchmidlinE, WannierT et al. Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nat Med 2006; 12: 790–2.
46. ZornerB, SchwabME. Anti-Nogo on the go: from animal models to a clinical trial. Ann N Y Acad Sci 2010; 1198: E22–34.
47. LiS, StrittmatterSM. Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 2003; 23: 4219–27.
48. SilverJ, MillerJH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5: 146–56.
49. CapecchiMR. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 2005; 6: 507–12.
50. SioudM. Main approaches to target discovery and validation. Methods Mol Biol 2007; 360: 1–12.
51. ZambrowiczBP, SandsAT. Knockouts model the 100 best-selling drugs–will they model the next 100? Nat Rev Drug Discov 2003; 2: 38–51.
52. SimonenM, PedersenV, WeinmannO, et al. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 2003; 38: 201–11.
53. ZhengB, HoC, LiS, et al. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 2003; 38: 213–24.
54. LeeJK, ChanAF, LuuSM, et al. Reassessment of corticospinal tract regeneration in Nogo-deficient mice. J Neurosci 2009; 29: 8649–54.
55. DimouL, SchnellL, MontaniL, et al. Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration. J Neurosci 2006; 26: 5591–603.
56. StewardO, ZhengB, BanosK, et al. Response to: Kim et al. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 38, 187–199. Neuron 2007; 54: 191–5.
57. BartschU, BandtlowCE, SchnellL, et al. Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS. Neuron 1995; 15: 1375–81.
58. JiB, CaseLC, LiuK, et al. Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury. Mol Cell Neurosci 2008; 39: 258–67.
59. SongXY, ZhongJH, WangX, et al. Suppression of p75NTR does not promote regeneration of injured spinal cord in mice. J Neurosci 2004; 24: 542–6.
60. NakamuraY, FujitaY, UenoM, et al. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. J Biol Chem 2010; 286: 1876–83.
61. LeeJK, GeoffroyCG, ChanAF, et al. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 2010; 66: 663–70.
62. CaffertyWB, DuffyP, HuebnerE, et al. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci 2010; 30: 6825–37.
63. RaineteauO, FouadK, BareyreFM, et al. Reorganization of descending motor tracts in the rat spinal cord. Eur J Neurosci 2002; 16: 1761–71.
64. CaffertyWB, StrittmatterSM. The Nogo–Nogo receptor pathway limits a spectrum of adult CNS axonal growth. J Neurosci 2006; 26: 12242–50.
65. BensonMD, RomeroMI, LushME, et al. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth. Proc Natl Acad Sci U S A 2005; 102: 10694–9.
66. ManittC, ColicosMA, ThompsonKM, et al. Widespread expression of netrin-1 by neurons and oligodendrocytes in the adult mammalian spinal cord. J Neurosci 2001; 21: 3911–22.
67. HataK, FujitaniM, YasudaY, et al. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol 2006; 173: 47–58.
68. De WinterF, OudegaM, LankhorstAJ, et al. Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 2002; 175: 61–75.
69. Moreau-FauvarqueC, KumanogohA, CamandE, et al. The transmembrane semaphorin Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and up-regulated after CNS lesion. J Neurosci 2003; 23: 9229–39.
70. GoldbergJL, VargasME, WangJT, et al. An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells. J Neurosci 2004; 24: 4989–99.
71. GoldshmitY, GaleaMP, WiseG, et al. Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J Neurosci 2004; 24: 10064–73.
72. SchachtrupC, LuP, JonesLL, et al. Fibrinogen inhibits neurite outgrowth via beta 3 integrin-mediated phosphorylation of the EGF receptor. Proc Natl Acad Sci U S A 2007; 104: 11814–19.
73. WinzelerAM, MandemakersWJ, SunMZ, et al. The lipid sulfatide is a novel myelin-associated inhibitor of CNS axon outgrowth. J Neurosci 2011; 31: 6481–92.
74. LowK, CulbertsonM, BradkeF, et al. Netrin-1 is a novel myelin-associated inhibitor to axon growth. J Neurosci 2008; 28: 1099–108.
75. KanekoS, IwanamiA, NakamuraM, et al. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 2006; 12: 1380–9.
76. BradburyEJ, MoonLD, PopatRJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636–40.
77. ShenY, TenneyAP, BuschSA, et al. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 2009; 326: 592–6.
78. BarrittAW, DaviesM, MarchandF, et al. Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 2006; 26: 10856–67.
79. BradburyEJ, McMahonSB. Spinal cord repair strategies: why do they work? Nat Rev Neurosci 2006; 7: 644–53.
80. MasseyJM, AmpsJ, ViapianoMS, et al. Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3. Exp Neurol 2008; 209: 426–45.
81. VoeltzGK, PrinzWA, ShibataY, et al. A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 2006; 124: 573–86.
82. LeeH, RaikerSJ, VenkateshK, et al. Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J Neurosci 2008; 28: 2753–65.
83. RaikerSJ, LeeH, BaldwinKT, et al. Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity. J Neurosci 2010; 30: 12432–45.
84. McGeeAW, YangY, FischerQS, et al. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 2005; 309: 2222–6.
85. SykenJ, GrandpreT, KanoldPO, et al. PirB restricts ocular-dominance plasticity in visual cortex. Science 2006; 313: 1795–800.
86. PizzorussoT, MediniP, BerardiN, et al. Reactivation of ocular dominance plasticity in the adult visual cortex. Science 2002; 298: 1248–51.
87. NeumannS, WoolfCJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999; 23: 83–91.
88. NeumannS, BradkeF, Tessier-LavigneM, et al. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002; 34: 885–93.
89. QiuJ, CaiD, DaiH, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002; 34: 895–903.
90. ParkKK, LiuK, HuY, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008; 322: 963–6.
91. LiuK, LuY, LeeJK, et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010; 13: 1075–81.
92. MaierIC, IchiyamaRM, CourtineG et al. Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury. Brain 2009; 132: 1426–40.

References

1. BerryM. Post-injury myelin-breakdown products inhibit axonal growth: an hypothesis to explain the failure of axonal regeneration in the mammalian central nervous system. Bibl Anat 1982; 23: 1–11.
2. CaroniP, SchwabME. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1988; 1: 85–96.
3. DomeniconiM, CaoZ, SpencerT, et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 2002; 35: 283–90.
4. LiuBP, FournierA, GrandPreT, et al. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science 2002; 297: 1190–3.
5. MiS, LeeX, ShaoZ, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004; 7: 221–8.
6. WangKC, KimJA, SivasankaranR, et al. p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 2002; 420: 74–8.
7. WongST, HenleyJR, KanningKC, et al. A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci 2002; 5: 1302–8.
8. AtwalJK, Pinkston-GosseJ, SykenJ, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 2008; 322: 967–70.
9. ChenMS, HuberAB, van der HaarME, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434–9.
10. GrandPreT, NakamuraF, VartanianT, et al. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 2000; 403: 439–44.
11. McKerracherL, DavidS, JacksonDL, et al. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 1994; 13: 805–11.
12. MukhopadhyayG, DohertyP, WalshFS, et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994; 13: 757–67.
13. PrinjhaR, MooreSE, VinsonM, et al. Inhibitor of neurite outgrowth in humans. Nature 2000; 403: 383–4.
14. BisbyMA, TetzlaffW, BrownMC. Cell body response to injury in motoneurons and primary sensory neurons of a mutant mouse, Ola (Wld), in which Wallerian degeneration is delayed. J Comp Neurol 1995; 359: 653–62.
15. BrownMC, BoothCM, LunnER, et al. Delayed response to denervation in muscles of C57BL/Ola mice. Neuroscience 1991; 43: 279–83.
16. BrownMC, LunnER, PerryVH. Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. J Neurobiol 1992; 23: 521–36.
17. PerryVH, BrownMC, LunnER. Very slow retrograde and Wallerian degeneration in the CNS of C57BL/Ola mice. Eur J Neurosci 1991; 3: 102–5.
18. CaroniP, SchwabME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106: 1281–8.
19. BregmanBS, Kunkel-BagdenE, SchnellL, et al. Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 1995; 378: 498–501.
20. SchnellL, SchwabME. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 1990; 343: 269–72.
21. SpillmannAA, BandtlowCE, LottspeichF, et al. Identification and characterization of a bovine neurite growth inhibitor (bNI-220). J Biol Chem 1998; 273: 19283–93.
22. JosephsonA, WidenfalkJ, WidmerHW, et al. NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. Exp Neurol 2001; 169: 319–28.
23. HuberAB, WeinmannO, BrosamleC, et al. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 2002; 22: 3553–67.
24. WangX, ChunSJ, TreloarH, et al. Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J Neurosci 2002; 22: 5505–15.
25. van de VeldeHJ, RoebroekAJ, SendenNH, et al. NSP-encoded reticulons, neuroendocrine proteins of a novel gene family associated with membranes of the endoplasmic reticulum. J Cell Sci 1994; 107: 2403–16.
26. OertleT, BussA, DoddD, et al. Membrane Topologies and Receptors of the Oligodendrocyte Protein Nogo–A. Program 333.10, Washington, DC: Society for Neuroscience, 2002.
27. FournierAE, GrandPreT, StrittmatterSM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409: 341–6.
28. PrinjhaRK, HillC, IrvingE, et al. Mapping the Functional Inhibitory Sites of Nogo – A. Discovery of Regulated Expression following Neuronal Injury. Program 333.12. Washington, DC: Society for Neuroscience, 2002.
29. GuptaSK, PodusloJF, MezeiC. Temporal changes in PO and MBP gene expression after crush-injury of the adult peripheral nerve. Brain Res 1988; 464: 133–41.
30. PotC, SimonenM, WeinmannO, et al. Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury. J Cell Biol 2002; 159: 29–35.
31. KimJE, LiS, GrandPreT, et al. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 2003; 38: 187–99.
32. ZhengB, HoC, LiS, et al. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 2003; 38: 213–24.
33. SimonenM, PedersenV, WeinmannO, et al. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 2003; 38: 201–11.
34. CrockerPR, ClarkEA, FilbinM, et al. Siglecs: a family of sialic-acid binding lectins. Glycobiology 1998; 8: v.
35. LaiC, BrowMA, NaveKA, et al. Two forms of 1B236/myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing. Proc Natl Acad Sci U S A 1987; 84: 4337–41.
36. SalzerJL, HolmesWP, ColmanDR. The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol 1987; 104: 957–65.
37. SalzerJL, PedrazaL, BrownM, et al. Structure and function of the myelin-associated glycoproteins. Ann N Y Acad Sci 1990; 605: 302–12.
38. TrappBD. Myelin-associated glycoprotein. Location and potential functions. Ann N Y Acad Sci 1990; 605: 29–43.
39. TrappBD, AndrewsSB, CootaucoC, et al. The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes. J Cell Biol 1989; 109: 2417–26.
40. FilbinMT. Myelin-associated glycoprotein: a role in myelination and in the inhibition of axonal regeneration? Curr Opin Neurobiol 1995; 5: 588–95.
41. QuarlesRH. Myelin-associated glycoprotein in development and disease. Dev Neurosci 1983; 6: 285–303.
42. LiC, TropakMB, GerlaiR, et al. Myelination in the absence of myelin-associated glycoprotein. Nature 1994; 369: 747–50.
43. MontagD, GieseKP, BartschU, et al. Mice deficient for the myelin-associated glycoprotein show subtle abnormalities in myelin. Neuron 1994; 13: 229–46.
44. FruttigerM, MontagD, SchachnerM, et al. Crucial role for the myelin-associated glycoprotein in the maintenance of axon-myelin integrity. Eur J Neurosci 1995; 7: 511–15.
45. TangS, QiuJ, NikulinaE, et al. Soluble myelin-associated glycoprotein released from damaged white matter inhibits axonal regeneration. Mol Cell Neurosci 2001; 18: 259–69.
46. TangS, WoodhallRW, ShenYJ, et al. Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration. Mol Cell Neurosci 1997; 9: 333–46.
47. LiM, ShibataA, LiC, et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J Neurosci Res 1996; 46: 404–14.
48. ShenYJ, DeBellardME, SalzerJL, et al. Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits axonal regeneration and branching. Mol Cell Neurosci 1998; 12: 79–91.
49. BartschU, BandtlowCE, SchnellL, et al. Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS. Neuron 1995; 15: 1375–81.
50. FilbinMT. The muddle with MAG. Mol Cell Neurosci 1996; 8: 84–92.
51. SchaferM, FruttigerM, MontagD, et al. Disruption of the gene for the myelin-associated glycoprotein improves axonal regrowth along myelin in C57BL/Wlds mice. Neuron 1996; 16: 1107–13.
52. KottisV, ThibaultP, MikolD, et al. Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J Neurochem 2002; 82: 1566–9.
53. HabibAA, MartonLS, AllwardtB, et al. Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse central nervous system. J Neurochem 1998; 70: 1704–11.
54. Vourc’hP, AndresC. Oligodendrocyte myelin glycoprotein (OMgp): evolution, structure and function. Brain Res Brain Res Rev 2004; 45: 115–24.
55. Vourc’hP, DessayS, MbarekO, et al. The oligodendrocyte-myelin glycoprotein gene is highly expressed during the late stages of myelination in the rat central nervous system. Brain Res Dev Brain Res 2003; 144: 159–68.
56. MikolDD, StefanssonK. A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes. J Cell Biol 1988; 106: 1273–9.
57. Vourc’hP, MoreauT, ArbionF, et al. Oligodendrocyte myelin glycoprotein growth inhibition function requires its conserved leucine-rich repeat domain, not its glycosylphosphatidyl-inositol anchor. J Neurochem 2003; 85: 889–97.
58. FournierAE, GouldGC, LiuBP, et al. Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci 2002; 22: 8876–83.
59. HuntD, MasonM, CampbellG, et al. Nogo receptor mRNA expression in intact and regenerating CNS neurons. Mol Cell Neurosci 2002; 20: 537.
60. HuntD, CoffinRS, AndersonPN. The Nogo receptor, its ligands and axonal regeneration in the spinal cord; a review. J Neurocytol 2002; 31: 93–120.
61. BartonWA, LiuBP, TzvetkovaD, et al. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. EMBO J 2003; 22: 3291–302.
62. HeXL, BazanJF, McDermottG, et al. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron 2003; 38: 177–85.
63. VinsonM, StrijbosPJ, RowlesA, et al. Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition. J Biol Chem 2001; 276: 20280–5.
64. VyasAA, PatelHV, FromholtSE, et al. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci U S A 2002; 99: 8412–17.
65. TangS, ShenYJ, DeBellardME, et al. Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site. J Cell Biol 1997; 138: 1355–66.
66. PignotV, HeinAE, BarskeC, et al. Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo-66 receptor. J Neurochem 2003; 85: 717–28.
67. VenkateshK, ChivatakarnO, LeeH, et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci 2005; 25: 808–22.
68. DostalerSM, RossGM, MyersSM, et al. Characterization of a distinctive motif of the low molecular weight neurotrophin receptor that modulates NGF-mediated neurite growth. Eur J Neurosci 1996; 8: 870–9.
69. CaiD, ShenY, De BellardM, et al. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 1999; 22: 89–101.
70. BandtlowC, DechantG. From cell death to neuronal regeneration, effects of the p75 neurotrophin receptor depend on interactions with partner subunits. Sci STKE 2004; 2004: pe24.
71. BarkerPA. p75NTR is positively promiscuous: novel partners and new insights. Neuron 2004; 42: 529–33.
72. RyffelB, MihatschMJ. TNF receptor distribution in human tissues. Int Rev Exp Pathol 1993; 34: 149–56.
73. EbadiM, BashirRM, HeidrickML, et al. Neurotrophins and their receptors in nerve injury and repair. Neurochem Int 1997; 30: 347–74.
74. ParkJB, YiuG, KanekoS, et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 2005; 45: 345–51.
75. ShaoZ, BrowningJL, LeeX, et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005; 45: 353–9.
76. NakamuraY, FujitaY, UenoM, et al. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury. J Biol Chem 2011; 286: 1876–83.
77. KimJE, LiuBP, ParkJH, et al. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron 2004; 44: 439–51.
78. McGeeAW, YangY, FischerQS, et al. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 2005; 309: 2222–6.
79. Syken, J, GrandpreT, KanoldPO, et al. PirB restricts ocular-dominance plasticity in visual cortex. Science 2006; 313: 1795–800.
80. PizzorussoT, MediniP, BerardiN, et al. Reactivation of ocular dominance plasticity in the adult visual cortex. Science 2002; 298: 1248–51.
81. LehmannM, FournierA, Selles-NavarroI, et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 1999; 19: 7537–47.
82. DerghamP, EllezamB, EssagianC, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22: 6570–7.
83. WintonMJ, DubreuilCI, LaskoD, et al. Characterization of new cell permeable C3-like proteins that inactivate Rho and stimulate neurite outgrowth on inhibitory substrates. J Biol Chem 2002; 277: 32820–9.
84. YamashitaT, HiguchiH, TohyamaM. The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol 2002; 157: 565–70.
85. SivasankaranR, PeiJ, WangKC, et al. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci 2004; 7: 261–8.
86. YamashitaT, TohyamaM. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 2003; 6: 461–7.
87. DechantG, BardeYA. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci 2002; 5: 1131–6.
88. LeeR, KermaniP, TengKK, et al. Regulation of cell survival by secreted proneurotrophins. Science 2001; 294: 1945–8.
89. Della-BiancaV, RossiF. ArmatoU, et al. Neurotrophin p75 receptor is involved in neuronal damage by prion peptide-(106–126). J Biol Chem 2001; 276: 38929–33.
90. PeriniG, Della-BiancaV, PolitiV, et al. Role of p75 neurotrophin receptor in the neurotoxicity by beta-amyloid peptides and synergistic effect of inflammatory cytokines. J Exp Med 2002; 195: 907–18.
91. KongH, BoulterJ, WeberJL, et al. An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors. J Neurosci 2001; 21: 176–85.
92. ChaoM, Casaccia-BonnefilP, CarterB, et al. Neurotrophin receptors: mediators of life and death. Brain Res Brain Res Rev 1998; 26: 295–301.
93. NykjaerA, LeeR, TengKK, et al. Sortilin is essential for proNGF-induced neuronal cell death. Nature 2004; 427: 843–8.
94. CasademuntE, CarterBD, BenzelI, et al. The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death. EMBO J 1999; 18: 6050–61.
95. SalehiAH, RouxPP, KubuCJ, et al. NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron 2000; 27: 279–88.
96. IrieS, HachiyaT, RabizadehS, et al. Functional interaction of Fas-associated phosphatase-1 (FAP-1) with p75(NTR) and their effect on NF-kappaB activation. FEBS Lett 1999; 460: 191–8.
97. MukaiJ, HachiyaT, Shoji-HoshinoS, et al. NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J Biol Chem 2000; 275: 17566–70.
98. YeX, MehlenP, RabizadehS, et al. TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction. J Biol Chem 1999; 274: 30202–8.
99. BilderbackTR, GrigsbyRJ, DobrowskyRT. Association of p75(NTR) with caveolin and localization of neurotrophin-induced sphingomyelin hydrolysis to caveolae. J Biol Chem 1997; 272: 10922–7.
100. MamidipudiV, LiX, WootenMW. Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B. J Biol Chem 2002; 277: 28010–18.
101. VolonteC, RossAH, GreeneLA. Association of a purine-analogue-sensitive protein kinase activity with p75 nerve growth factor receptors. Mol Biol Cell 1993; 4: 71–8.
102. WangJJ, TasinatoA, EthellDW, et al. Phosphorylation of the common neurotrophin receptor p75 by p38beta2 kinase affects NF-kappaB and AP-1 activities. J Mol Neurosci 2000; 15: 19–29.
103. ChittkaA, ArevaloJC, Rodriguez-GuzmanM, et al. The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E. J Cell Biol 2004; 164: 985–96.
104. YangB, SlonimskyJD, BirrenSJ. A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nat Neurosci 2002; 5: 539–45.
105. FurshpanEJ, MacLeishPR, O’LaguePH, et al. Chemical transmission between rat sympathetic neurons and cardiac myocytes developing in microcultures: evidence for cholinergic, adrenergic, and dual-function neurons. Proc Natl Acad Sci U S A 1976; 73: 4225–9.
106. LockhartST, TurrigianoGG, BirrenSJ. Nerve growth factor modulates synaptic transmission between sympathetic neurons and cardiac myocytes. J Neurosci 1997; 17: 9573–82.
107. DerghamP, EllezamB, EssagianC, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22: 6570–7.
108. FournierAE, TakizawaBT, StrittmatterSM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci 2003; 23: 1416–23.
109. NiederostB, OertleT, FritscheJ, et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 2002; 22: 10368–76.
110. AizawaH, WakatsukiS, IshiA., et al. Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat Neurosci 2001; 4: 367–73.
111. HsiehSH, FerraroGB, FournierAE. Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and Slingshot phosphatase. J Neurosci 2006; 26: 1006–15.
112. MimuraF, YamagishiS, ArimuraN, et al. Myelin-associated glycoprotein inhibits microtubule assembly by a Rho-kinase-dependent mechanism. J Biol Chem 2006; 281: 15970–9.
113. AlabedYZ, PoolM, Ong ToneS, et al. Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition. J Neurosci 2007; 27: 1702–11.
114. PerdigotoAL, ChaudhryN, BarnesGN, et al. A novel role for PTEN in the inhibition of neurite outgrowth by myelin-associated glycoprotein in cortical neurons. Mol Cell Neurosci 2011; 46: 235–44.
115. HuangDW, McKerracherL, BraunPE, et al. A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord. Neuron 1999; 24: 639–47.
116. GrandPreT, LiS, StrittmatterSM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 2002; 417: 547–51.
117. AlberiniCM, GhirardiM, HuangYY, et al. A molecular switch for the consolidation of long-term memory: cAMP-inducible gene expression. Ann N Y Acad Sci 1995; 758: 261–86.
118. FreyU, HuangYY, KandelER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 1993; 260: 1661–4.
119. WongST, AthosJ, FigueroaXA, et al. Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP. Neuron 1999; 23: 787–98.
120. WuZL, ThomasSA, VillacresEC, et al. Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci U S A 1995; 92: 220–4.
121. ByrneJH, KandelER. Presynaptic facilitation revisited: state and time dependence. J Neurosci 1996; 16: 425–35.
122. CastellucciVF, KandelER, SchwartzJH, et al. Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A 1980; 77: 7492–6.
123. CastellucciVF, NairnA, GreengardP, et al. Inhibitor of adenosine 3’:5’-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia. J Neurosci 1982; 2: 1673–81.
124. MilnerB, SquireLR, KandelER. Cognitive neuroscience and the study of memory. Neuron 1998; 20: 445–68.
125. SongH, MingG, HeZ, et al. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 1998; 281: 1515–18.
126. SongHJ, MingGL, PooMM. cAMP-induced switching in turning direction of nerve growth cones. Nature 1997; 388: 275–9.
127. CaiD, QiuJ, CaoZ, et al. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. 2001; J Neurosci 21: 4731–9.
128. ShearerMC, NiclouSP, BrownD, et al. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways. Mol Cell Neurosci 2003; 24: 913–25.
129. MonsulNT, GeisendorferAR, HanPJ, et al. Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve. Exp Neurol 2004; 186: 124–33.
130. WatanabeM, TokitaY, KatoM, et al. Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized beta ganglion cells in cat retina. Neuroscience 2003; 116: 733–42.
131. RichardsonPM, IssaVM. Peripheral injury enhances central regeneration of primary sensory neurones. Nature 1984; 309: 791–3.
132. RichardsonPM, VergeVM. The induction of a regenerative propensity in sensory neurons following peripheral axonal injury. J Neurocytol 1986; 15: 585–94.
133. NeumannS, WoolfCJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injuryNeuron 1999; 23: 83–91.
134. NeumannS, BradkeF, Tessier-LavigneM, et al. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002; 34: 885–93.
135. QiuJ, CaiD, DaiH, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002; 34: 895–903.
136. LuP, YangH, JonesLL, et al. Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J Neurosci 2004; 24: 6402–9.
137. NikulinaE, TidwellJL, DaiHN, et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 2004; 101: 8786–90.
138. PearseDD, PereiraFC, MarcilloAE, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med 2004; 10: 610–16.
139. GaoY, NikulinaE, MelladoW, et al. Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci 2003; 23: 11770–7.
140. CaiD, DengK, MelladoW, et al. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron 2002; 35: 711–19.
141. Kepka-LenhartD, MistrySK, WuG, et al. Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages? Am J Physiol Regul Integr Comp Physiol 2000; 279: R2237–42.
142. LiH, MeiningerCJ, HawkerJR Jr, et al. Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells. Am J Physiology Endocrinol Metab 2001; 280: E75–82.
143. DengK, HeH, QiuJ, et al. Increased synthesis of spermidine as a result of upregulation of arginase I promotes axonal regeneration in culture and in vivo. J Neurosci 2009; 29: 9545–52.
144. CaffertyWB, McGeeAW, StrittmatterSM. Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends Neurosci 2008; 31: 215–20.
145. ReichardtLF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1545–64.
146. BorasioGD, MarkusA, WittinghoferA, et al. Involvement of ras p21 in neurotrophin-induced response of sensory, but not sympathetic neurons. J Cell Biol 1993; 121: 665–72.
147. CoskerKE, EickholtBJ. Phosphoinositide 3-kinase signalling events controlling axonal morphogenesis. Biochem Soc Trans 2007; 35: 207–10.
148. MarkusA, PatelTD, SniderWD. Neurotrophic factors and axonal growth. Curr Opin Neurobiol 2002; 12: 523–31.
149. MarkusA, ZhongJ, SniderWD. Raf and akt mediate distinct aspects of sensory axon growth. Neuron 2002; 35: 65–76.
150. ZhouFQ, WalzerM, WuYH, et al. Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism. J Cell Sci 2006; 119: 2787–96.
151. ParkKK, LiuK, HuY, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008; 322: 963–66.
152. ZhouJ, WulfkuhleJ, ZhangH, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A 2007; 104: 16158–63.
153. GuertinDA, SabatiniDM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9–22.
154. MingG, SongH, BerningerB, et al. Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance. Neuron 1999; 23: 139–48.
155. ForcetC, SteinE, PaysL, et al. Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation. Nature 2002; 417: 443–7.
156. MingGL, WongST, HenleyJ, et al. Adaptation in the chemotactic guidance of nerve growth cones. Nature 2002; 417: 411–18.
157. ShekarabiM, KennedyTE. The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1. Mol Cell Neurosci 2002; 19: 1–17.
158. GraefIA, WangF, CharronF, et al. Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 2003; 113: 657–70.
159. TongJ, KilleenM, StevenR, et al. Netrin stimulates tyrosine phosphorylation of the UNC-5 family of netrin receptors and induces Shp2 binding to the RCM cytodomain. J Biol Chem 2001; 276: 40917–25.
160. MingGL, SongHJ, BerningerB, et al. cAMP-dependent growth cone guidance by netrin-1. Neuron 1997; 19: 1225–35.
161. HongK, NishiyamaM, HenleyJ, et al. Calcium signalling in the guidance of nerve growth by netrin-1. Nature 2000; 403: 93–8.
162. NishiyamaM, HoshinoA, TsaiL, et al. Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning. Nature 2003; 424: 990–5.
163. PasterkampRJ, VerhaagenJ. Emerging roles for semaphorins in neural regeneration. Brain Res Brain Res Rev 2001; 35: 36–54.
164. PasterkampRJ, AndersonPN, VerhaagenJ. Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A. Eur J Neurosci 2001; 13: 457–71.
165. PasterkampRJ, GigerRJ, RuitenbergMJ, et al. Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS. Mol Cell Neurosci 1999; 13: 143–66.
166. PasterkampRJ, GigerRJ, VerhaagenJ. Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration. Exp Neurol 1998; 153: 313–27.
167. PasterkampRJ, De WinterF, HoltmaatAJ, et al. Evidence for a role of the chemorepellent semaphorin III and its receptor neuropilin-1 in the regeneration of primary olfactory axons. J Neurosci 1998; 18: 9962–76.
168. BroseK, BlandKS, WangKH, et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 1999; 96: 795–806.
169. KiddT, BlandKS, GoodmanCS. Slit is the midline repellent for the robo receptor in Drosophila. Cell 1999; 96: 785–94.
170. LiHS, ChenJH, WuW, et al. Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell 1999; 96: 807–18.
171. WongK, RenXR, HuangYZ, et al. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell 2001; 107: 209–21.
172. MarillatV, CasesO, Nguyen-Ba-CharvetKT, et al. Spatiotemporal expression patterns of slit and robo genes in the rat brain. J Comp Neurol 2002; 442: 130–55.
173. HaginoS, IsekiK, MoriT, et al. Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain. Glia 2003; 42: 130–8.
174. KnollB, DrescherU. Ephrin-As as receptors in topographic projections. Trends Neurosci 2002; 25: 145–9.
175. WahlS, BarthH, CiossekT, et al. Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J Cell Biol 2000; 149: 263–70.
176. BundesenLQ, ScheelTA, BregmanBS, et al. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 2003; 23: 7789–800.
177. JanisLS, CassidyRM, KromerLF. Ephrin-A binding and EphA receptor expression delineate the matrix compartment of the striatum. J Neurosci 1999; 19: 4962–71.
178. MirandaJD, WhiteLA, MarcilloAE, et al. Induction of Eph B3 after spinal cord injury. Exp Neurol 1999; 156: 218–22.
179. WillsonCA, Irizarry-RamirezM, GaskinsHE, et al. Upregulation of EphA receptor expression in the injured adult rat spinal cord. Cell Transplant 2002; 11: 229–39.
180. WinslowJW, MoranP, ValverdeJ, et al. Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation. Neuron 1995; 14: 973–81.
181. KnollB, IsenmannS, KilicE, et al. Graded expression patterns of ephrin-As in the superior colliculus after lesion of the adult mouse optic nerve. Mech Dev 2001; 106: 119–27.
182. McLaughlinT, O’LearyDD. Functional consequences of coincident expression of EphA receptors and ephrin-A ligands. Neuron 1999; 22: 636–9.
183. BarrettCP, GuthL, DonatiEJ, et al. Astroglial reaction in the gray matter lumbar segments after midthoracic transection of the adult rat spinal cord. Exp Neurol 1981; 73: 365–77.
184. YangHY, LieskaN, ShaoD, et al. Proteins of the intermediate filament cytoskeleton as markers for astrocytes and human astrocytomas. Mol Chem Neuropathol 1994; 21: 155–76.
185. GalloV, BertolottoA, LeviG. The proteoglycan chondroitin sulfate is present in a subpopulation of cultured astrocytes and in their precursors. Dev Biol 1987; 123: 282–5.
186. JonesLL, MargolisRU, TuszynskiMH. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 2003; 182: 399–411.
187. McKeonRJ, JurynecMJ, BuckCR. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J Neurosci 1999; 19: 10778–88.
188. TangX, DaviesJE, DaviesSJ. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res 2003; 71: 427–44.
189. McKeonRJ, SchreiberRC, RudgeJS, et al. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 1991; 11: 3398–411.
190. NiederostBP, ZimmermannDR, SchwabME, et al. Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans. J Neurosci 1999; 19: 8979–89.
191. Smith-ThomasLC, Fok-SeangJ, StevensJ, et al. An inhibitor of neurite outgrowth produced by astrocytes. J Cell Sci 1994; 107: 1687–95.
192. DaviesSJ, GoucherDR, DollerC, et al. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 1999; 19: 5810–22.
193. AlilainWJ, HornKP, HuH, et al. Functional regeneration of respiratory pathways after spinal cord injury. Nature 2011; 475: 196–200.
194. BradburyEJ, MoonLD, PopatRJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636–40.
195. BorisoffJF, ChanCC, HiebertGW, et al. Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 2003; 22: 405–16.
196. MonnierPP, SierraA, SchwabJM, et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 2003; 22: 319–30.

References

1. GoritzC, DiasDO, TomilinN, et al. A pericyte origin of spinal cord scar tissue. Science 2011; 333: 238–42.
2. MillerRH, RaffMC. Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. J Neurosci 1984; 4: 585–92.
3. EngLF. Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 1985; 8: 203–14.
4. ParriHR, GouldTM, CrunelliV. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci 2001; 4: 803–12.
5. KangJ, JiangL, GoldmanSA, et al. Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat Neurosci 1998; 1: 683–92.
6. BlomstrandF, AbergND, ErikssonPS, et al. Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions. Neuroscience 1999; 92: 255–65.
7. RakicP. Neuron-glial relationship during granule cell migration in the developing cerebellar cortex. A Golgi and electronmicroscopic study in Maccacus rhesus. J Comp Neurol 1971; 141: 238–312.
8. TalbottJF, CaoQ, EnzmannGU, et al. Schwann cell-like differentiation by adult oligodendrocyte precursor cells following engraftment into the demyelinated spinal cord is BMP-dependent. Glia 2006; 54: 147–59.
9. NakazawaE, IshikawaH. Ultrastructural observations of astrocyte end-feet in the rat central nervous system. J Neurocytol 1998; 27: 431–40.
10. AbbottNJ, RevestPA, RomeroIA. Astrocyte-endothelial interaction: physiology and pathology. Neuropathol Appl Neurobiol 1992; 18: 424–33.
11. XuJ, LingEA. Studies of the ultrastructure and permeability of the blood–brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. J Anat 1994; 184: 227–37.
12. YuWP, CollariniEJ, PringleNP, et al. Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube. Neuron 1994; 12: 1353–62.
13. AguirreAA, ChittajalluR, BelachewS, et al. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol 2004; 165: 575–89.
14. AraqueA, SanzgiriRP, ParpuraV, et al. Astrocyte-induced modulation of synaptic transmission. Can J Physiol Pharmacol 1999; 77: 699–706.
15. BacciA, VerderioC, PravettoniE, et al. The role of glial cells in synaptic function. Philos Trans R Soc Lond B Biol Sci 1999; 354: 403–9.
16. BenarrochEE. Neuron–astrocyte interactions: partnership for normal function and disease in the central nervous system. Mayo Clin Proc 2005; 80: 1326–38.
17. BerryM, IbrahimM, CarlileJ, et al. Axon-glial relationships in the anterior medullary velum of the adult rat. J Neurocytol 1995; 24: 965–83.
18. RaffMC, MillerRH, NobleM. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 1983; 303: 390–6.
19. RiversLE, YoungKM, RizziM, et al. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 2008; 11: 1392–401.
20. WatanabeT, RaffMC. Retinal astrocytes are immigrants from the optic nerve. Nature 1988; 332: 834–7.
21. BandoY, TakakusakiK, ItoS, et al. Differential changes in axonal conduction following CNS demyelination in two mouse models. Eur J Neurosci 2008; 28: 1731–42.
22. KessarisN, FogartyM, IannarelliP, et al. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci 2006; 9: 173–9.
23. RaffMC. Glial cell diversification in the rat optic nerve. Science 1989; 243: 1450–5.
24. MillerRH. Regulation of oligodendrocyte development in the vertebrate CNS. Prog Neurobiol 2002; 67: 451–67.
25. PfeifferSE, WarringtonAE, BansalR. The oligodendrocyte and its many cellular processes. Trends Cell Biol 1993; 3: 191–7.
26. RaffMC, MirskyR, FieldsKL, et al. Galactocerebroside is a specific cell surface antigenic marker for oligodendrocytes in culture. Nature 1978; 274: 813–16.
27. RaffMC, AbneyER, MillerRH. Two glial cell lineages diverge prenatally in rat optic nerve. Dev Biol 1984; 106: 53–60.
28. NishiyamaA, LinX-H, GieseN, et al. Interaction between NG2 proteoglycan and PDGF aReceptor on O2A progenitor cells is required for optimal response to PDGF. J Neurosci Res 1996; 43: 315–30.
29. RichardsonWD, PringleN, MosleyMJ et al. A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 1988; 53: 309–19.
30. SommerI, SchachnerM. Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: an immunocytological study in the central nervous system. Dev Biol 1981; 83: 311–27.
31. BansalR, StefanssonK, PfeifferSE. Proligodendroblast antigen (POA), a developmental antigen expressed by A007/O4-positive oligodendrocyte progenitors prior to the appearance of sulfatide and galactocerebroside. J Neurochem 1992; 58: 2221–9.
32. KondoT, RaffM. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 2000; 289: 1754–7.
33. BoglerO, WrenD, BarnettSC, et al. Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Proc Natl Acad Sci U S A 1990; 87: 6368–72.
34. JacobsonM. Developmental Neurobiology. New York, NY: Plenum Press, 1978.
35. ReynoldsBA, WeissS. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992; 255: 1707–10.
36. RowitchD. Glial specification in the vertebrate neural tube. Nat Rev Neurosci 2004; 5: 409–19.
37. WarfBC, Fok-SeangJ, MillerRH. Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord. J Neurosci 1991; 11: 2477–88.
38. OnoK, BansalR, PayneJ, et al. Early development and dispersal of oligodendrocyte precursors in the embyonic chick spinal cord. Development 1995; 121: 1743–54.
39. PringleNP, RichardsonWD. A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. Development 1993; 117: 525–33.
40. OrentasDM, MillerRH. The origin of spinal cord oligodendrocytes is dependent on local influences from the notochord. Dev Biol 1996; 177: 43–53.
41. JessellT. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 2000; 1: 20–9.
42. PringleNP, YuW, GuthrieS, et al. Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Dev Biol 1996; 177: 30–42.
43. FogartyM, RichardsonWD, KessarisN. A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development 2005; 132: 1951–9.
44. CaiJ, QiY, HuX, et al. Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of on Nkx6 regulation and Shh signaling. Neuron 2005; 45: 41–53.
45. PringleNP, GuthrieS, LumsdenA, et al. Dorsal spinal cord neuroepithelium generates astrocytes but not oligodendrocytes. Neuron 1998; 20: 883–93.
46. FancySP, BaranziniSE, ZhaoC, et al. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev 2009; 23: 1571–85.
47. MillerRH, DinsioKJ, WangR-Z, et al. Patterning of spinal cord oligodendrocyte development by dorsally derived BMP4. J Neurosci Res 2004; 76: 9–19.
48. SpasskyN, Goujet-ZalcC, ParmantierE, et al. Multiple restricted origin of oligodendrocytes. J Neurosci 1998; 18: 8331–43.
49. GaoL, MillerRH. Specification of optic nerve oligodendrocyte precursors by retinal ganglion cell axons. J Neurosci 2006; 26: 7619–28.
50. Perez VillagesEM, OlivierC, SpasskyN, et al. Early specification of oligodendrocytes in the chick embryonic brain. Dev Biol 1999; 216: 98–113.
51. TimsitS, MartinezS, AllinquantB, et al. Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. J Neurosci 1995; 15: 1012–24.
52. DakuboGD, BeugST, MazerolleCJ, et al. Control of glial precursor cell development in the mouse optic nerve by sonic hedgehog from retinal ganglion cells. Brain Res 2008; 1228: 27–42.
53. TripathiRB, ClarkeLE, BurzomatoV, et al. Dorsally and ventrally derived oligodendrocytes have similar electrical properties but myelinate preferred tracts. J Neurosci 2011; 31: 6809–19.
54. TsaiH-H, MillerRH. Glial cell migration directed by axon guidance cues. Trends Neurosci 2002; 25: 173–5.
55. TsaiHH, MacklinWB, MillerRH. Distinct modes of migration position oligodendrocyte precursors for localized cell division in the developing spinal cord. J Neurosci Res 2009; 87: 3320–30.
56. JarjourAA, ManittC, MooreSW, et al. Netrin1 is a chemorepellent for oligodendrocyte precursor cells in the embryonic spinal cord. J Neurosci 2003; 23: 68–72.
57. LiL, LundkvistA, AnderssonD, et al. Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 2008; 28: 468–81.
58. SilverJ, MillerJH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5: 1393–7.
59. LittleAR, O’CallaghaJP. Astrogliosis in the adult and developing CNS: is there a role for proinflammatory cytokines? Neurotoxicology 2001; 22: 607–18.
60. Nieto-SampedroM, SanetoRP, de VellisJ, et al. The control of glial populations in brain: changes in astrocyte mitogenic and morphogenic factors in response to injury. Brain Res 1985; 343: 320–8.
61. EngLF, GhirnikarRS. GFAP and astrogliosis. Brain Pathol 1994; 4: 229–37.
62. GuenardV, FrischG, WoodPM. Effects of axonal injury on astrocyte proliferation and morphology in vitro: implications for astrogliosis. Exp Neurol 1996; 137: 175–90.
63. SykovaE, VargovaL, ProkopovaS, et al. Glial swelling and astrogliosis produce diffusion barriers in the rat spinal cord. Glia 1999; 25: 56–70.
64. FullerML, DeChantAK, RothsteinB, et al. Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions. Ann Neurol 2007; 62: 288–300.
65. FaulknerJR, HerrmannJE, WooMJ, et al. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24: 2143–55.
66. SmithGM, RutishauserU, SilverJ, et al. Maturation of astrocytes in vitro alters the extent and molecular basis of neurite outgrowth. Dev Biol 1990; 138: 377–90.
67. DaviesSJ, ShihCH, NobleM, et al. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury. PLoS One 2011; 6: e17328.
68. DaviesJE, HuangC, ProschelC et al. Astrocytes derived from glial-restricted precursors promote spinal cord repair. J Biol 2006; 5: 7.
69. KomitovaM, SerwanskiDR, LuQR, et al. NG2 cells are not a major source of reactive astrocytes after neocortical stab wound injury. Glia 2011; 59: 800–9.
70. BuschSA, HornKP, CuascutFX, et al. Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury. J Neurosci 2010; 30: 255–65.
71. FilbinMT. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 2003; 4: 703–13.
72. McTigueDM, WeiP, StokesBT. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 2001; 21: 3392–400.
73. FranklinRJ, GilsonJM, FranceschiniIA, et al. Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS. Glia 1996; 17: 217–24.
74. BarnettSC, RiddellJS. Olfactory ensheathing cell transplantation as a strategy for spinal cord repair–what can it achieve? Nat Clin Pract Neurol 2007; 3: 152–61.
75. FairlessR, BarnettSC. Olfactory ensheathing cells: their role in central nervous system repair. Int J Biochem Cell Biol 2005; 37: 693–9.
76. FranklinRJ, BarnettSC. Do olfactory glia have advantages over Schwann cells for CNS repair? J Neurosci Res 1997; 50: 665–72.
77. ZawadzkaM, RiversLE, FancySP, et al. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell 2010; 6: 578–90.

References

1. ChauvetN, PrietoM, AlonsoG. Tanycytes present in the adult rat mediobasal hypothalamus support the regeneration of monoaminergic axons. Exp Neurol 1998; 151: 1–13.
2. Monti GraziadeiGA, KarlanMS, BernsteinJJ, et al. Reinnervation of the olfactory bulb after section of the olfactory nerve in monkey (Saimiri sciureus). Brain Res 1980; 189: 343–54.
3. MorrisonEE, CostanzoRM. Regeneration of olfactory sensory neurons and reconnection in the aging hamster central nervous system. Neurosci Lett 1995; 198: 213–17.
4. FenrichKK, RosePK. Spinal interneuron axons spontaneously regenerate after spinal cord injury in the adult feline. J Neurosci 2009; 29: 12145–58.
5. Ramón y Cajal. Degeneration and Regeneration of the Nervous System. MayRM, trans. London: Oxford University Press, 1928.
6. LiY, RaismanG. Sprouts from cut corticospinal axons persist in the presence of astrocytic scarring in long-term lesions of the adult rat spinal cord. Exp Neurol 1995; 134: 102–11.
7. WindleWF, ChambersWW. Regeneration in the spinal cord of the cat and dog. J Comp Neurol 1950; 93: 241–58.
8. WindleWF, ClementeCD, ChambersWW. Inhibition of formation of a glial barrier as a means of permitting a peripheral nerve to grow into the brain. J Comp Neurol 1952; 96: 359–69.
9. ClementeCD, WindleWF. Regeneration of severed nerve fibers in the spinal cord of the adult cat. J Comp Neurol 1954; 101: 691–731.
10. ClementeCD. The regeneration of peripheral nerves inserted into the cerebral cortex and the healing of cerebral lesions. J Comp Neurol 1958; 109: 123–43.
11. BrookGA, PlateD, FranzenR, et al. Spontaneous longitudinally oriented axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat. J Neurosci Res 1998; 53: 51–65.
12. FaulknerJR, HerrmannJE, WooMJ, et al. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2003; 24: 2143–55.
13. GoritzC, DiasDO, TomilinN, et al. A pericyte origin of spinal cord scar tissue. Science 2011; 333: 238–42.
14. BignamiA, DahlD. The astroglial response to stabbing. Immunofluorscence studies with antibodies to astrocyte-specific protein (GFA) in mammalian and submammalian vertebrates. Neuropathol Appl Neurobiol 1976; 2: 99–110.
15. FitchMT, SilverJ. Beyond the glial scar: cellular and molecular mechanisms by which glial cells contribute to CNS regenerative failure. In TuszynskiMH, KordowerJH, eds. CNS Regeneration: Basic Science and Clinical Advances. San Diego, CA: Academic Press, 1999; 55–88.
16. BarretCP, GuthL, DonatiEJ, et al. Astroglial reaction in the gray matter of lumbar segments after midthoracic transection of the adult rat spinal cord. Exp Neurol 1981; 73: 365–77.
17. BignamiA, DahlD. Astrocyte-specific protein and neuroglial differentiation. An immunofluorescence study with antibodies to the glial fibrillary acidic protein. J Comp Neurol 1974; 153: 27–38.
18. EngLF. Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 1985; 8: 203–14.
19. YangHY, LieskaN, ShaoD, et al. Proteins of the intermediate filament cytoskeleton as markers for astrocytes and human astrocytomas. Mol Chem Neuropathol 1994; 21: 155–76.
20. BushTG, PuvanachandraN, HornerCH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 1999; 23: 297–308.
21. HerrmannJE, ImuraT, SongB, et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 2008; 28: 7231–43.
22. KadoyaK, TsukadaS, LuP, et al. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 2009; 64: 165–72.
23. HouleJD. Demonstration of the potential for chronically injured neurons to regenerate axons into intraspinal peripheral nerve grafts. Exp Neurol 1991; 113: 1–9.
24. KobayashiNR, FanDP, GiehlKM, et al. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Talpha1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997; 17: 9583–95.
25. KwonBK, LiuJ, MessererC, et al. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 2002; 99: 3246–51.
26. HouleJD, JinY. Chronically injured supraspinal neurons exhibit only modest axonal dieback in response to a cervical hemisection lesion. Exp Neurol 2001; 169: 208–17.
27. TomVJ, DollerCM, SilverJ. Promoting regeneration of dystrophic axons. Soc Neurosci (Abstr) 2002; 635: 14.
28. BuschSA, HornKP, SilverDJ, et al. Overcoming macrophage-mediated axonal dieback following CNS injury. J Neurosci 2009; 29: 9967–76.
29. KerschensteinerM, SchwabME, LichtmanJW, et al. In vivo imaging of axonal degeneration and regeneration in the injured spinal cord. Nat Med 2005; 11: 572–7.
30. PrestonE, WebsterJ, SmallD. Characteristics of sustained blood–brain barrier opening and tissue injury in a model for focal trauma in the rat. J Neurotrauma 2001; 18: 83–92.
31. FitchMT, DollerC, CombsCK, et al. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 1999; 19: 8182–98.
32. NikicI, MerklerD, SorbaraC, et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 2011; 17: 495–9.
33. LagordC, BerryM, LoganA. Expression of TGFβ2 but not TGFβ1 correlates with the deposition of scar tissue in the lesioned spinal cord. Mol Cell Neurosci 2002; 20: 69–92.
34. AsherRA, MorgensternDA, FidlerPS, et al. Neurocan is up-regulated in injured brain and in cytokine-treated astrocytes. J Neurosci 2000; 20: 2427–38.
35. MoonLDF, FawcettJW. Reduction in CNS scar formation without concomitant increase in axon regeneration following treatment of adult rat brain with a combination of antibodies to TGFβ1 and β2. Eur J Neurosci 2001; 14: 1667–77.
36. KohtaM, KohmuraE, YamashitaT. Inhibition of TGF-beta1 promotes functional recovery after spinal cord injury. Neurosci Res 2009; 65: 393–401.
37. SchachtrupC, RyuJK, HelmrickMJ, et al. Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-β after vascular damage. J Neurosci 2010; 30: 5843–54.
38. GiulianD, WoodwardJ, YoungDG, et al. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 1988; 8: 2485–90.
39. YongVW, MoumdjianR, YongFP, et al. γ-Interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci U S A 1991; 88: 7016–20.
40. LoganA, FrautschySA, GonzalezAM, et al. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one if its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci 1992; 12: 3828–37.
41. MocchettiI, RabinSJ, ColangeloAM, et al. Increased basic fibroblast growth factor expression following contusive spinal cord injury. Exp Neurol 1996; 141: 154–64.
42. DiProsperoNA, MeinersS, GellerHM. Inflammatory cytokines interact to modulate extracellular matrix and astrocytic support of neurite outgrowth. Exp Neurol 1997; 148: 628–39.
43. MiyakeT, HattoriT, FukudaM, et al. Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex. Brain Res 1988; 451: 133–8.
44. AlexanderJK, PopovichPG. Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration. Prog Brain Res 2009; 175: 125–37.
45. DaviesSJA, FieldPM, RaismanG. Regeneration of cut adult axons fails even in the presence of continuous aligned glial pathways. Exp Neurol 1996; 142: 203–16.
46. DaviesSJA, FitchMT, MembergSP, et al. Regeneration of adult axons in white matter tracts of the central nervous system. Nature 1997; 390: 680–3.
47. PindzolaRR, DollerC, SilverJ. Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during development and after root and sciatic nerve lesions. Dev Biol 1993; 156: 34–48.
48. McQuarrieIG, GrafsteinB. Axon outgrowth enhanced by a previous nerve injury. Arch Neurol 1973; 29: 53–5.
49. KernsJM, DanielsenN, HolmquistB, et al. The influence of predegeneration on regeneration through peripheral nerve grafts in the rat. Exp Neurol 1993; 122: 28–36.
50. SjobergJ, KanjeM. The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect. Brain Res 1990; 529: 79–84.
51. HoffmanPN. A conditioning lesion induces changes in gene expression and axonal transport that enhance regeneration by increasing the intrinsic growth state of axons. Exp Neurol 2010; 223: 11–18.
52. YleraB, ErturkA, HellalF, et al. Chronically CNS-injured adult sensory neurons gain regenerative competence upon a lesion of their peripheral axon. Curr Biol 2009; 19: 930–6.
53. QiuJ, CaiD, DaiH, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002; 34: 895–903.
54. NeumannS, BradkeF, Tessier-LavigneM, et al. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002; 34: 885–93.
55. FenrichKK, RosePK. Axons with highly branched terminal regions successfully regenerate across spinal midline transections in the adult cat. J Comp Neurol 2011; 519: 3240–58.
56. ParkKK, LiuK, HuY, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008; 322: 963–6.
57. LiuK, LuY, LeeJK, et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010; 13: 1075–81.
58. FawcettJW, AsherRA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49: 377–91.
59. RhodesKE, RaivichG, FawcettJW. The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages, and inflammation-associated cytokines. Neuroscience 2006; 140: 87–100.
60. SuZ, YuanY, ChenJ, et al. Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-alpha. J Neurotrauma; 2011; 28: 1089–100.
61. SiebertJR, StelznerDJ, OsterhoutDJ. Chondroitinase treatment following spinal contusion injury increases migration of oligodendrocyte precursor cells. Exp Neurol 2011; 231: 19–29.
62. BuschSA, HamiltonJA, HornKP, et al. Multipotent adult progenitor cells prevent macrophage-mediated axonal dieback and promote regrowth after spinal cord injury. J Neurosci 2011; 31: 944–53.
63. Di MaioA, SkubaA, HimesBT, et al. In vivo imaging of dorsal root regeneration: rapid immobilization and presynaptic differentiation at the CNS/PNS border. J Neurosci 2011; 31: 4569–82.
64. RudgeJS, SilverJ. Inhibition of neurite outgrowth on astroglial scars in vitro. J Neurosci 1990; 10: 3594–603.
65. BahrM, PrzyrembelC, BastmeyerM. Astrocytes from adult rat optic nerves are nonpermissive for regenerating retinal ganglion cell axons. Exp Neurol 1995; 131: 211–20.
66. Le RouxPD, RehTA. Reactive astroglia support primary dendritic but not axonal outgrowth from mouse cortical neurons in vitro. Exp Neurol 1996; 137: 49–65.
67. SmithG, MillerRH, SilverJ. Changing role of forebrain astrocytes during development, regenerative failure, and induced regeneration upon transplantation. J Comp Neurol 1986; 251: 23–43.
68. SmithG, SilverJ. Transplantation of immature and mature astrocytes and their effect on scar formation in the lesioned central nervous system. Prog Brain Res 1988; 78: 353–61.
69. SmithG, MillerRH. Immature type-1 astrocytes suppress glial scar formation, are motile and interact with blood vessels. Brain Res 1991; 543: 111–22.
70. JinY, NeuhuberB, SinghA, et al. Transplantation of human glial restricted progenitors and derived astrocytes into a contusion model of spinal cord injury. J Neurotrauma 2011; 28: 579–94.
71. HaasC, NeuhuberB, YamagamiT, et al. Phenotypic analysis of astrocytes derived from glial restricted prescursors and their impact on axon regeneration. Exp Neurol 2012; 233: 717–32.
72. DaviesJE, HuangC, ProschelC, et al. Astrocytes derived from glial-restricted precursor promote spinal cord repair. J Biol 2006; 5: 7.
73. DaviesJE, ShihCH, NobleM, et al. Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury. PLoS One 2011; 6: e17328.
74. FilousAR, MillerJH, Coulson-ThomasYM, et al. Immature astrocytes promote CNS axonal regeneration when combined with chondroitinase ABC. Dev Neurobiol 2010; 70: 826–41.
75. HornKP, BuschSA, HawthorneAL, et al. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 2008; 28: 9330–41.
76. KigerlKA, GenselJC, AnkenyDP, et al. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the mouse spinal cord. J Neurosci 2009; 29: 13435–44.
77. BovolentaP, WandosellF, Nieto-SampedroM. Characterization of a neurite outgrowth inhibitor expressed after CNS injury. Eur J Neurosci 1993; 5: 454–65.
78. GeisertEE, BidanestDJ, Del MarN, et al. Up-regulation of a keratan sulfate proteoglycan following cortical injury in neonatal rats. Int J Dev Neurosci 1996; 14: 257–67.
79. HuberAB, SchwabME. Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem 2000; 381: 407–19.
80. JonesLL, MargolisRU, TuszynskiMH. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 2003; 182: 399–411.
81. McKeonRJ, SchreiberRC, RudgeJS, et al. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 1991; 11: 3398–411.
82. TangX, DaviesJE, DaviesSJA. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican, V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res 2003; 71: 427–44.
83. CanningDR, HökeA, MalemudCJ, et al. A potent inhibitor of neurite outgrowth that predominates in the extracellular matrix of reactive astrocytes. Int J Dev Neurosci 1996; 14: 153–75.
84. Wyss-CorayT, FengL, MasliahE, et al. Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta 1. Am J Pathol 1995; 147: 53–67.
85. GalloV, BertolottoA. Extracellular matrix of cultured glial cells: Selective expression of chondroitin 4-sulfate by type-2 astrocytes and their progenitors. Exp Cell Res 1990; 187: 211–23.
86. GalloV, BertolottoA, LeviG. The proteoglycan chondroitin sulfate is present in a subpopulation of cultured astrocytes and in their precursors. Dev Biol 1987; 123: 282–5.
87. Johnson-GreenPC, DowKE, RiopelleRJ. Characterization of glycosaminoglycans produced by primary astrocytes in vitro. Glia 1991; 4: 314–21.
88. GrimpeB, SilverJ. The extracellular matrix in axon regeneration. Prog Brain Res 2002; 137: 333–49.
89. MargolisRK, MargolisRU. Nervous tissue proteoglycans. Experientia 1993; 49: 429–46.
90. MorgensternDA, AsherRA, FawcettJW. Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 2002; 137: 313–32.
91. McKeonRJ, JurynecMJ, BuckCR. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J Neurosci 1999; 19: 10778–88.
92. Katoh-SembaR, MatsudaM, KatoK, et al. Chondroitin sulphate proteoglycans in the rat brain: candidates for axon barriers of sensory neurons and the possible modification by laminin of their actions. Eur J Neurosci 1995; 7: 613–21.
93. SnowDM, SteindlerDA, SilverJ. Molecular and cellular characterization of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier. Dev Biol 1990; 138: 359–76.
94. ColeGJ, McCabeCF. Identification of a developmentally regulated keratan sulfate proteoglycan that inhibits cell adhesion and neurite outgrowth. Neuron 1991; 7: 1007–18.
95. WuDY, SchneiderGE, SilverJ, et al. A role for tectal midline glia in the unilateral containment of retinocollicular axons. J Neurosci 1998; 18: 8344–55.
96. BrittisPA, CanningDR, SilverJ. Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science 1992; 255: 733–6.
97. JhaveriS. Midline glia of the tectum: a barrier for developing retinal axons. Prespect Dev Neurobiol 1993; 1: 237–43.
98. BeckerCG, BeckerT. Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. J Neurosci 2002; 22: 842–53.
99. ChungK, ShumDK, ChanS. Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos. J Comp Neurol 2000; 417: 153–63.
100. HyndsDL, SnowDM. Neurite outgrowth inhibition by chondroitin sulfate proteoglycan stalling/stopping exceeds turning in human neuroblastoma growth cones. Exp Neurol 1999; 160: 244–55.
101. SnowDM, LemmonV, CarrinoDA, et al. Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 1990; 109: 111–30.
102. DouCL, LevineJM. Inhibtion of neurite growth by the NG2 chondroitin sulfate proteoglycan. J Neurosci 1994; 14: 7616–28.
103. SnowDM, BrownEM, LetourneauPC. Growth cone behavior in the presence of soluble chondroitin sulfate proteoglycan (CSPG), compared to behavior on CSPG bound to laminin or fibronectin. Int J Dev Neurosci 1996; 14: 331–49.
104. JonesLL, YamaguchiY, StallcupWB, et al. NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 2002; 22: 2792–803.
105. MoonLDF, AsherRA, RhodesKE, et al. Relationship between sprouting axons, proteoglycans and glial cells following unilateral nigrostriatal axotomy in the adult rat. Neuroscience 2002; 109: 101–17.
106. CanningDR, McKeonRJ, DeWittDA, et al. β-amyloid of Alzheimer’s disease induces reactive gliosis that inhibits axonal outgrowth. Exp Neurol 1993; 124: 289–98.
107. Smith-ThomasLC, Fok-SeangJ, StevensJ, et al. An inhibitor of neurite outgrowth produced by astrocytes. J Cell Sci 1994; 107: 1687–95.
108. McKeonRJ, HökeA, SilverJ. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 1995; 136: 32–43.
109. ShenY, TenneyAP, BuschSA, et al. PTP sigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor for neural regeneration. Science 2009; 326: 592–6.
110. LiS, FisherD, XingB, et al. LAR is a functional receptor for CSPG axon growth inhibitors. J Neurosci 2013 [In Press]
111. FryEJ, ChagnonMJ, López-ValesR, et al. Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice. Glia 2010; 58: 423–33.
112. LangBT, CreggJM, WengYL, et al. The LAR family of pro-synaptic proteins help mediate glial scar induced axonal regeneration failure following spinal cord injury. Soc Neurosci (Abstr) 2011; 892: 15/EE7.
113. HawthorneAL, HuH, KunduB, et al. The unusual response of serotonergic neurons after CNS injury: lack of axonal dieback and enhanced sprouting within the inhibitory environment of the glial scar. J Neurosci 2011; 31: 5605–16.
114. ColesCH, ShenY, TenneyAP, et al. Proteoglycan-specific molecular switch for RPTP sigma clustering and neuronal extension. Science 2011; 332: 484–8.
115. SnowDM, LetourneauPC. Neurite outgrowth on a step gradient of chondroitin sulfate proteoglycan (CS-PG). J Neurobiol 1992; 23: 322–36.
116. InmanDM, StewardO. Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice. J Comp Neurol 2003; 462: 431–49.
117. Feraboli-LohnherrD, OrsalD, YakovleffA, et al. Recovery of locomotor activity in the adult chronic spinal rat after sublesional transplantation of embryonic nervous cells: specific role of serotonergic neurons. Exp Brain Res 1997; 113: 443–54.
118. RibottaMG, ProvncherJ, Feraboli-LohnherrD, et al. Activation of locomotion in adult chronic spinal rats is achieved by transplantation of embryonic raphe cells reinnervating a precise lumbar level. J Neurosci 2000; 20: 5144–52.
119. PasterkampRJ, GigerRJ, RuitenbergMJ, et al. Expression of the gene encoding the chemorepellent semaphoring III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS. Mol Cell Neurosci 1999; 13: 143–66.
120. De WinterF, OudegaM, LankhorstAJ, et al. Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 2002; 175: 61–75.
121. PasterkampRJ, AndersonPN, VerhaagenJ. Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A. Eur J Neurosci 2001; 13: 457–71.
122. KanekoS, IwanamiA, NakamuraM, et al. A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 2006; 12: 1380–9.
123. BundesonLQ, ScheelTA, BregmanBS, et al. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 2003; 23: 7789–800.
124. BroseK, Tessier-LavigneM. Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr Opin Neurobiol 2000; 10: 95–102.
125. RoncaF, AndersonJS, PaechV, et al. Characterization of slit protein interactions with glypican-1. J Biol Chem 2001; 276: 29141–7.
126. HaginoS, IsekiK, MoriT, et al. Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain. Glia 2003; 42: 130–8.
127. ApostalovaI, IrintchevA, SchachnerM. Tenascin-R restricts posttraumatic remodeling of motorneuron innervation and functional recovery after spinal cord injury in adult mice. J Neurosci 2006; 26: 7849–59.
128. ProbstmeierR, StichelCC, MullerHW, et al. Chondroitin sulfates expressed on oligodendrocyte-derived tenascin-R are involved in neural cell recognition. Functional implications during CNS development and regeneration. J Neurosci Res 2000; 60: 21–36.
129. EddlestonM, MuckeL. Molecular profile of reactive astrocytes–implications for their role in neurologic disease. Neurosci 1993; 54: 15–36.
130. LiesiP, KaakkolaS, DahlD, et al. Laminin is induced in astrocytes of adult brain by injury. EMBO J 1984; 3: 683–86.
131. FrisénJ, HægerstrandA, RislingM, et al. Spinal axons in central nervous system scar tissue are closely related to laminin-immunoreactive astrocytes. Neuroscience 1995; 65: 293–304.
132. BernsteinJJ, GetzR, JeffersonM, et al. Astrocytes secrete basal lamina after hemisection of rat spinal cord. Brain Res 1985: 327: 135–41.
133. RislingM, FriedK, LindåH, et al. Regrowth of motor axons following spinal cord lesions: distribution of laminin and collagen in the CNS scar tissue. Brain Res Bull 1993; 30: 405–14.
134. KawajaMD, GageFH. Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor. Neuron 1991; 7: 1019–30.
135. HirschS, BährM. Immunocytochemical characterization of reactive optic nerve astrocytes and meningeal cells. Glia 1999; 26: 36–46.
136. Moreno-FloresMT, Martín-AparicioE, SalineroO, et al. Fibronectin modulation by Aβ amyloid peptide (25–35) in cultured astrocytes of newborn rat cortex. Neurosci Lett 2001; 314: 87–91.
137. MahlerM, Ben-AriY, RepresaA. Differential expression of fibronectin, tenascin-C and NCAMs in cultured hippocampal astrocytes activated by kainite, bacterial lipopolysaccharide or basic fibroblast growth factor. Brain Res 1997; 775: 63–73.
138. DusartI, MorelMP, WehrléR, et al. Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar. J Comp Neurol 1999; 408: 399–418.
139. CostaS, PlanchenaultT, Charriere-BertrandC, et al. Astroglial permissivity for neuritic outgrowth in neuron–astrocyte cocultures depends on regulation of laminin bioavailability. Glia 2002; 37: 105–13.
140. MenetV, Gimenéz y RibottaM, ChauvetN, et al. Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression. J Neurosci 2001; 21: 6147–58.
141. ZhangH, ChangM, HansenCN, et al. Role of matrix metalloproteinases and therapeutic benefits of their inhibition in spinal cord injury. Neurotherapeutics 2011; 8: 206–20.
142. HsuJY, BourguignonLY, AdamsCM, et al. Matrix metalloproteinase 9 facilitates glial scar formation in the injured spinal cord. J Neurosci 2008; 8: 13467–77.
143. PizziMA, CroweMJ. Matrix metalloproteinases and proteoglycans in axonal regeneration. Exp Neurol 2007; 204: 496–511.
144. HsiehHL, WangHH, WuWB, et al. Transforming growth factor beta 1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-kB pathways. J Neuroinflammation 2010; 7: 88.
145. NobleLJ, DonovanF, IgarashiT, et al. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci 2002; 2: 7526–35.
146. LiuH, ShubayevVI. Matrix metalloproteinase-9 controls proliferation of NG2+ progenitor cells immediately after spinal cord injury. Exp Neurol 2011; 231: 236–46.
147. DaviesSJA, GoucherDR, DollerC, et al. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 1999; 19: 5810–22.
148. TomVJ, DollerCM, SilverJ. Fibronectin is critical for axonal regeneration in white matter. Soc Neurosci (Abstr) 2003; 42: 12.
149. ZaiLJ, WrathallJR. Cell proliferation and replacement following contusive spinal cord injury. Glia 2005; 50: 247–57.
150. LytleJM, ViciniS, WrathallJR. Phenotypic changes in NG2+ cells after spinal cord injury. J Neurotrauma 2006; 23: 1726–38.
151. BuschSA, HornKP, CuascutFX, et al. Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury. J Neurosci 2010; 30: 255–65.
152. CarlstedtT. Regenerating axons form nerve terminals at astrocytes. Brain Res 1985; 347: 188–91.
153. BerglesDE, RobertsJD, SomogyiP, et al. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 2000; 405: 187–91.
154. LinSC, BerglesDE. Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nat Neurosci 2004; 7: 24–32
155. FilousAR, EvansTA, LangBT, et al. Dystrophic axons form synapse-like connections on NG2+ cells after spinal cord injury. Soc Neurosci (Abstr) 2012; 47: 13.
156. BrücknerG, BringmannA, HärtigW, et al. Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain. Exp Brain Res 1998; 121: 300–10.
157. MoonLDF, AsherRA, RhodesKE, et al. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 2001; 4: 465–6.
158. BradburyEJ, MoonLDF, PopatRJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636–40.
159. CaggianoAO, ZimberMP, GangulyA, et al. Chondroitinase ABC 1 improves locomotor function after spinal cord contusion injury in the rat. Soc Neurosci (Abstr) 2003; 744: 5.
160. JeffersonSC, TesterNJ, HowlandDR. Chondroitinase ABC promotes recovery of adaptive limb movements and enhances axonal growth caudal to a spinal hemisection. J Neurosci 2011; 31: 5710–20.
161. GrimpeB, SilverJ. A novel DNA-enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted DRG axons to regenerate beyond lesions in the spinal cord. J Neurosci 2004; 24: 1393–7.
162. WangD, IchiyamaRM, ZhaoR, et al. Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury. J Neurosci 2011; 31: 9332–44.
163. MayesDA, HouleJD. Combined use of matrix degrading enzymes and neurotrophic factors to facilitate axonal regeneration after spinal cord injury. Soc Neurosci (Abstr) 2003; 245: 1.
164. XuXM, GuenardV, KleitmanN, et al. Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 1995; 351: 145–60.
165. AlilainWJ, HornKP, HuH, et al. Functional regeneration of respiratory pathways after spinal cord injury. Nature 2011; 475: 196–200.
166. OudegaM, HaggT. Nerve growth factor promotes regeneration of sensory axons into adult rat spinal cord. Exp Neurol 1996; 140: 218–29.
167. OudegaM, HaggT. Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord. Brain Res 1999; 818: 431–8.
168. BradburyEJ, KhemaniS, KingVR, et al. NT-3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord. Eur J Neurosci 1999; 11: 3873–83.
169. RamerMS, PriestlyJV, McMahonSB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312–16.
170. RamerMS, DuraisingamI, PriestleyJV, et al. Two-tiered inhibition of axon regeneration at the dorsal root entry zone. J Neurosci 2001; 21: 2651–60.
171. RamerMS, BishopT, DockeryP, et al. Neurotrophin-3-mediated regeneration and recovery of proprioception following dorsal rhizotomy. Mol Cell Neurosci 2002; 19: 239–49.
172. RomeroMI, RangappaN, GarryMG, et al. Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy. J Neurosci 2001; 21: 8408–16.
173. ZhangY, DijkhuizenPA, AndersonPN, et al. NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats. J Neuroci Res 1998; 54: 554–62.
174. AltoLT, HavtonLA, ConnerJM, et al. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nat Neurosci 2009; 12: 1106–13.
175. CondicML. Adult neuronal regeneration induced by transgenic integrin expression. J Neurosci 2001; 21: 4782–8.
176. BorisoffJF, ChanCCM, HiebertGW, et al. Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 2003; 22: 405–16.
177. DerghamP, EllezamB, EssagianC, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22: 6570–7.
178. MonnierPP, SierraA, SchwabJM, et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 2003; 22: 319–30.
179. YinY, CuiQ, LiY, et al. Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci 2003; 23: 2284–93.
180. SteinmetzMP, TomVJ, MillerJH, et al. A novel combinatorial strategy which dramatically influences axon regeneration across a model of the glial scar in vitro. Soc Neurosci (Abstr) 2003; 880: 4.
181. LeibingerM, MullerA, AndreadakiA, et al. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci 2009; 29: 14334–41.
182. SilverJ, MillerJH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5: 146–56.

References

1. NimmerjahnA, KirchhoffF, HelmchenF. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005; 308: 1314–18.
2. RansohoffRM, PerryVH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 2009; 27: 119–45.
3. StreitWJ. Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 2002; 40: 133–9.
4. TakeuchiO, AkiraS. Pattern recognition receptors and inflammation. Cell 2010; 140: 805–20.
5. BalistreriCR, Colonna-RomanoG, LioD, et al. TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases. J Clin Immunol 2009; 29: 406–15.
6. Di VirgilioF, CerutiS, BramantiP, et al. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci 2009; 32: 79–87.
7. HusemannJ, LoikeJD, AnankovR, et al. SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia 2002; 40: 195–205.
8. NathanC, DingA. Nonresolving inflammation. Cell 2010; 140: 871–82.
9. SaijoK, WinnerB, CarsonCT, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 2009; 137: 47–59.
10. AkiyamaH, BargerS, BarnumS, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging 2000; 21: 383–421.
11. Wyss-CorayT, LoikeJD, BrionneTC, et al. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 2003; 9: 453–7.
12. CartierL, HartleyO, Dubois-DauphinM, et al. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005; 48: 16–42.
13. RebeckG W, HoeHS, MoussaCE. [beta]-Amyloid1–42 gene transfer model exhibits intraneuronal amyloid, gliosis, tau phosphorylation, and neuronal loss. J Biol Chem 2010; 285: 7440–6.
14. PereiraC, AgostinhoP, MoreiraPI, et al. Alzheimer’s disease-associated neurotoxic mechanisms and neuroprotective strategies. Curr Drug Targets CNS Neurol Disord 2005; 4: 383–403.
15. KitazawaM, YamasakiTR, LaFerlaFM. Microglia as a potential bridge between the amyloid beta-peptide and tau. Ann N Y Acad Sci 2004; 1035: 85–103.
16. StewartCR, StuartLM, WilkinsonK, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 2010; 11: 155–61.
17. SchroderK, TschoppJ. The inflammasomes. Cell 2010; 140: 821–32.
18. SchroderK, ZhouR, TschoppJ. The NLRP3 inflammasome: a sensor for metabolic danger?Science 2010; 327: 296–300.
19. HalleA, HornungV, PetzoldGC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 2008; 9: 857–65.
20. NeeperM, SchmidtAM, BrettJ, et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 1992; 267: 14998–5004.
21. SchmidtAM, ViannaM, GerlachM, et al. Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem 1992; 267: 14987–97.
22. YanSD, ChenX, FuJ, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature 1996; 382: 685–91.
23. RamasamyR, YanSF, SchmidtAM. RAGE: therapeutic target and biomarker of the inflammatory response–the evidence mounts. J Leukoc Biol 2009; 86: 505–12.
24. BuG. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 2009; 10: 333–44.
25. YoshiyamaY, HiguchiM, ZhangB, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007; 53: 337–51.
26. LiY, LiuL, BargerSW, et al. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J Neurosci 2003; 23: 1605–11.
27. QuintanillaRA, OrellanaDI, Gonzalez-BillaultC, et al. Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway. Exp Cell Res 2004; 295: 245–57.
28. SaezTE, PeharM, VargasM, et al. Astrocytic nitric oxide triggers tau hyperphosphorylation in hippocampal neurons. In Vivo 2004; 18: 275–80.
29. CooksonMR, BandmannO. Parkinson’s disease: insights from pathways. Hum Mol Genet 2010; 19: R21–7.
30. HealyDG, Abou-SleimanPM, LeesAJ, et al. Tau gene and Parkinson’s disease: a case-control study and meta-analysis. J Neurol Neurosurg Psychiatry 2004; 75: 962–5.
31. MartinER, ScottWK, NanceMA, et al. Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. JAMA 2001; 286: 2245–50.
32. BennerEJ, BanerjeeR, ReynoldsAD, et al. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLoS One 2008; 3: e1376.
33. KuhnDM, Francescutti-VerbeemDM, ThomasDM. Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Ann N Y Acad Sci 2006; 1074: 31–41.
34. ReynoldsAD, KadiuI, GargSK, et al. Nitrated alpha-synuclein and microglial neuroregulatory activities. J Neuroimmune Pharmacol 2008; 3: 59–74.
35. WilmsH, RosenstielP, SieversJ, et al. Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson’s disease. FASEB J 2003; 17: 500–2.
36. HirschEC, HunotS. Neuroinflammation in Parkinson’s disease: a target for neuroprotection?Lancet Neurol 2009; 8: 382–97.
37. CastanoA, HerreraAJ, CanoJ,et al. Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 1998; 70: 1584–92.
38. HunterRL, DragicevicN, SeifertK, et al. Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 2007; 100: 1375–86.
39. KimWG, MohneyRP, WilsonB, et al. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 2000; 20: 6309–16.
40. BrochardV, CombadiereB, PrigentA, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 2009; 119: 182–92.
41. McGeerPL, McGeerEG. Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 2002; 26: 459–70.
42. LetiembreM, LiuY, WalterS, et al. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol Aging 2009; 30: 759–68.
43. NguyenMD, D’AigleT, GowingG, et al. Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J Neurosci 2004; 24: 1340–9.
44. NadeauS, RivestS. Role of microglial-derived tumor necrosis factor in mediating CD14 transcription and nuclear factor kappa B activity in the brain during endotoxemia. J Neurosci 2000; 20: 3456–68.
45. NguyenMD, JulienJP, RivestS. Induction of proinflammatory molecules in mice with amyotrophic lateral sclerosis: no requirement for proapoptotic interleukin-1beta in neurodegeneration. Ann Neurol 2001; 50: 630–9.
46. LiuY, HaoW, DawsonA, et al. Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J Biol Chem 2009; 284: 3691–9.
47. YiangouY, FacerP, DurrenbergerP, et al. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 2006; 6: 12.
48. AmitI, GarberM, ChevrierN, et al. Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 2009; 326: 257–63.
49. UranishiH, TetsukaT, YamashitaM, et al. Involvement of the pro-oncoprotein TLS (translocated in liposarcoma) in nuclear factor-kappa B p65-mediated transcription as a coactivator. J Biol Chem 2001; 276: 13395–401.
50. RaoulC, EstevezAG, NishimuneH, et al. Motoneuron death triggered by a specific pathway downstream of Fas potentiation by ALS-linked SOD1 mutations. Neuron 2002; 35: 1067–83.
51. BarbeitoLH, PeharM, CassinaP, et al. A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 2004; 47: 263–74.
52. PeharM, CassinaP, VargasMR, et al. Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J Neurochem 2004; 89: 464–73.
53. VargasMR, PeharM, Diaz-AmarillaPJ, et al. Transcriptional profile of primary astrocytes expressing ALS-linked mutant SOD1. J Neurosci Res 2008; 86: 3515–25.
54. TikkaTM, VartiainenNE, GoldsteinsG, et al. Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease. Brain 2002; 125: 722–31.
55. KangJ, RivestS. MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J Cell Biol 2007; 179: 1219–30.
56. MantovaniS, GarbelliS, PasiniA, et al. Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process. J Neuroimmunol 2009; 210: 73–9.
57. BanerjeeR, MosleyRL, ReynoldsAD et al. Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS One 2008; 3: e2740.
58. BeersDR, HenkelJS, ZhaoW, et al. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci U S A 2008; 105: 15558–63.
59. ChiuIM, ChenA, ZhengY, et al. T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci U S A 2008; 105: 17913–18.
60. HarrisonJK, JiangY, ChenS, et al. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci U S A 1998; 95: 10896–901.
61. MeucciO, FatatisA, SimenAA, et al. Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A 1998; 95: 14500–5.
62. MizunoT, KawanokuchiJ, NumataK,et al. Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res 2003; 979: 65–70.
63. CombadiereC, FeumiC, RaoulW, et al. CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest 2007; 117: 2920–8.
64. CardonaAE, PioroEP, SasseME, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 2006; 9: 917–24.
65. DenesA, FerencziS, HalaszJ, et al. Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. J Cereb Blood Flow Metab 2008; 28: 1707–21.
66. FuhrmannM, BittnerT, JungCK, et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer’s disease. Nat Neurosci 2010; 13: 411–13.
67. LeeS, VarvelNH, KonerthME, et al. CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer’s disease mouse models. Am J Pathol 2010; 177: 2549–62.
68. BhaskarK, KonerthM, Kokiko-CochranON, et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 2010; 68: 19–31.
69. MadernaP, YonaS, PerrettiM, et al. Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone-treated macrophages and annexin-derived peptide Ac(2–26). J Immunol 2005; 174: 3727–33.
70. MorimotoK, JanssenWJ, FesslerMB, et al. Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease. J Immunol 2006; 176: 7657–65.
71. Probst-CousinS, KowolikD, KuchelmeisterK, et al. Expression of annexin-1 in multiple sclerosis plaques. Neuropathol Appl Neurobiol 2002; 28: 292–300.
72. KnottC, SternG, WilkinGP. Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 2000; 16: 724–39.
73. de CoupadeC, AjueborMN, Russo-MarieF, et al. Cytokine modulation of liver annexin 1 expression during experimental endotoxemia. Am J Pathol 2001; 159: 1435–43.
74. SzaboC, ThiemermannC, WuCC, et al. Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo. Proc Natl Acad Sci U S A 1994; 91: 271–5.
75. McArthurS, CristanteE, PaternoM, et al. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. J Immunol 2010; 185: 6317–28.

References

1. TengS, HempsteadB. Neurotrophins and their receptors: signaling trios in complex biological systems. Cell Mol Life Sci 2004; 61: 35–48.
2. LeeR, KermaniP, TengKK, et al. Regulation of cell survival by secreted proneurotrophins. Science 2001; 294: 1945–8.
3. TengKK, FeliceS, KimT, et al. Understanding proneurotrophin actions: recent advances and challenges. Dev Neurobiol 2010; 70: 350–9.
4. DechantG, BardeY-A. The neurotrophin receptor p75ntr: novel functions and implications for diseases of the nervous system. Nat Neurosci 2002; 5: 1131–6.
5. SchectersonLC, BothwellM. Neurotrophin receptors: old friends with new partners. Dev Neurobiol 2010; 70: 332–8.
6. CowanWM, HamburgerV, Levi-MontalciniR. The path to the discovery of nerve growth factor. Ann Rev Neurosci 2001; 24: 551–600.
7. Levi-MontalciniRThe nerve growth factor 35 years later. Science 1987; 237: 1154–62.
8. HuangEJ, ReichardtLF. Neurotrophins: roles in neuronal development and function. Ann Rev Neurosci 2001; 24: 677–736.
9. SegalRA. Selectivity in neurotrophin signaling: theme and variations. Ann Rev Neurosci 2003; 26: 299–330.
10. GreeneLS, TischlerAS. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A 1976; 73: 2424–8.
11. ChaoMV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4: 299–309.
12. ReichardtLF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1545–64.
13. MarkusA, PatelTD, SniderWD. Neurotrophic factors and axonal growth. Curr Opin Neurobiol 2002; 12: 523–31.
14. CowleyS, PatersonH, KempP, et al. Activation of MAP kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 1994; 77: 841–52.
15. Bar-SagiD, HallA. Ras and Rho GTPases: a family reunion. Cell 2000; 103: 227–38.
16. KaplanDR, MillerFD. Neurotrophin signal; transduction in the nervous system. Curr Opin Neurobiol 2000; 10: 381–91.
17. DohertyP, WilliamsG, WilliamsEJ. CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade. Mol Cell Neurosci 2000; 16: 283–95.
18. CampenotRB, MacInnisBL. Retrograde transport of neurotrophins: fact and function. J Neurobiol 2004; 58: 217–29.
19. ZweifelLS, KuruvillaR, GintyDD.Functions and mechanisms of retrograde neurotrophin signaling. Nat Rev Neurosci 2005; 6: 615–25.
20. HoweCL, VallettaJS, RusnakAS, et al. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway. Neuron 2001; 32: 801–14.
21. ShaoY, AkmentinW, Toledo-AralJJ, et al. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes. J Cell Biol 2002; 157: 679–91.
22. DelcroixJD, VallettaJS, WuC, et al. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals. Neuron 2003; 39: 69–84.
23. PhilippidouP, ValdezG, AkmentinW, et al. Trk retrograde signaling requires persistent, Pincher-directed endosomes. Proc Natl Acad Sci U S A 2011; 108: 852–7.
24. GalloG, LetourneauPC. Localized sources of neurotrophins initiate axon collateral sprouting. J Neurosci 1998; 18: 5403–14.
25. HempsteadBL. The many faces of p75NTR. Curr Opin Neurobiol 2002; 12: 260–7.
26. YamashitaT, TuckerKL, BardeY-A. Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron 1999; 24: 585–93.
27. HallA. Rho GTPases and the actin cytoskeleton. Science 1998; 279: 509–14.
28. WangKC, KimJA, SivasankaranR, et al. p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 2002; 420: 74–8.
29. YamashitaT, HiguchiH, Tohyama, M. The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol 2002; 157: 565–70.
30. AtwalJK, Pinkston-GosseJ, SykenJ, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 2008; 322: 967–70.
31. NjaA, PurvesD. The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea-pig. J Physiol 1978; 277: 55–75.
32. BoydJG, GordonT. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Mol Neurobiol 2003; 27: 277–324.
33. TerenghiG. Peripheral nerve regeneration and neurotrophic factors. J Anat 1999; 194: 1–14.
34. KoliatsosVE, ClatterbuckRE, WinslowJW, et al. Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 1993; 10: 359–67.
35. SendtnerM, HoltmannB, KolbeckR, et al. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 1992; 360: 757–9.
36. YanQ, Elliott, JL, MathesonC, et al. Influences of neurotrophins on mammalian motoneurons in vivo. J Neurobiol 1993; 24: 1555–77.
37. VejsadaR, TsengJL, LindsayRM, et al. Synergistic but transient rescue effects of BDNF and GDNF on axotomized neonatal motoneurons. Neuroscience 1998; 84: 129–39.
38. HottingerAF, AzzouzM, DeglonN, et al. Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. J Neurosci 2000; 20: 5587–93.
39. MendellLM, TaylorJS, JohnsonRD, et al. Rescue of motoneuron and muscle afferent function in cats by regeneration into skin. II. Ia-motoneuron synapse. J Neurophysiol 1995; 73: 662–73.
40. MunsonJB, SheltonDL, McMahonSB. Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and rescue by exogenous neurotrophins after axotomy. J Neurosci 1997; 17: 470–6.
41. MendellLM, JohnsonRD, MunsonJB. Neurotrophin modulation of the monosynaptic reflex after peripheral nerve transection. J Neurosci 1999; 19: 3162–70.
42. BaydyukM, RussellT, LiaoGY, et al. TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons. Proc Natl Acad Sci U S A 2011; 108: 1669–74.
43. FunakoshiH, FrisenJ, BarbanyG, et al. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol 1993; 123: 455–65.
44. HammarbergH, PiehlF, RislingM, et al. Differential regulation of trophic factor receptor mRNAs in spinal motoneurons after sciatic nerve transection and ventral root avulsion in the rat. J Comp Neurol 2000; 426: 587–601.
45. NovikovaLN, NovikovLN, KellerthJO. Differential effects of neurotrophins on neuronal survival and axonal regeneration after spinal cord injury in adult rats. J Comp Neurol 2002; 452: 255–63.
46. GordonT, TyremanN, RajiMA. The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci 2011; 31: 5325–34.
47. KuceraJ, FanG, JaenischR, et al. Dependence of developing group Ia afferents on neurotrophin-3. J Comp Neurol 1995; 363: 307–20.
48. OakleyRA, GarnerAS, LargeTH, et al. Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. Development 1995; 121: 1341–50.
49. ChenHH, HippenmeyerS, ArberS, et al. Development of the monosynaptic stretch reflex circuit. Curr Opin Neurobiol 2003; 13: 96–102.
50. ShneiderNA, MentisGZ, SchustakJ, et al. Functionally reduced sensorimotor connections form with normal specificity despite abnormal muscle spindle development: the role of spindle-derived neurotrophin 3. J Neurosci 2009; 29: 4719–35.
51. BergmanE, JohnsonH, ZhangX, et al. Neuropeptides and neurotrophin receptor mRNAs in primary sensory neurons of aged rats. J Comp Neurol 1996; 375: 303–19.
52. CurtisR, TonraJR, StarkJL, et al. Neuronal injury increases retrograde axonal transport of the neurotrophins to spinal sensory neurons and motor neurons via multiple receptor mechanisms. Mol Cell Neurosci 1998; 12: 105–18.
53. HökeA, RedettR, HameedH, et al. Schwann cells express motor and sensory phenotypes that regulate axon regeneration. J Neurosci 2006; 26: 9646–55.
54. BradburyEJ, KhemaniS, KingVR, et al. NT-3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord. Eur J Neurosci 1999; 11: 3873–83.
55. LindsayRM. Role of neurotrophins and Trk receptors in the development and maintenance of sensory neurons: an overview. Philos Trans R Soc Lond B Biol Sci 1996; 351: 365–73.
56. MendellLM. Neurotrophic factors and the specification of neural function. Neuroscientist 1995; 1: 26–34.
57. McMahonSB, ArmaniniMP, LingLH, et al. Expression and coexpression of Trk receptors in subpopulations of adult primary sensory neurons projecting to identified peripheral targets. Neuron 1994; 12: 1161–71.
58. RamerMS, PriestleyJV, McMahonSB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312–16.
59. RamerMS, BishopT, DockeryP, et al. Neurotrophin-3-mediated regeneration and recovery of proprioception following dorsal rhizotomy. Mol Cell Neurosci 2002; 19: 239–49.
60. WangR, KingT, OssipovMH, et al. Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury. Nat Neurosci 2008; 11: 488–96.
61. AltoLT, HavtonLA, ConnerJM, et al. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nat Neurosci 2009; 422: 1106–13.
62. ZhouL, BaumgartnerBJ, Hill-FelbergSJ, et al. Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J Neurosci 2003; 23: 1424–31.
63. TanAM, PetruskaJC, MendellLM, et al. Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state. Exp Neurol 2007; 206: 257–68.
64. McTigueDM, HornerPJ, StokesBT, et al. Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 1998; 18: 5354–65.
65. BonnerJF, ConnorsTM, SilvermanWF, et al. Grafted neural progenitors integrate and restore synaptic connectivity across the injured spinal cord. J Neurosci 2011; 31: 4675–86.
66. Keyvan-FouladiN, RaismanG, LiY. Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats. J Neurosci 2003; 23: 9428–34.
67. Bretzner, F., Liu, J., Currie, E., et al. Undesired effects of a combinatorial treatment for spinal cord injury–transplantation of olfactory ensheathing cells and BDNF infusion to the red nucleus. Eur J Neurosci 2008; 28: 1795–807.
68. KobayashiNR, FanD, GiehlKM, et al. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and T_1- tubulin mRNA expression and promote axonal regeneration. J Neurosci 1997: 17: 9583–95.
69. BrockJH, RosenzweigES, BleschA, et al. Local and remote growth factor effects after primate spinal cord injury. J Neurosci 2010; 30: 9728–37.
70. KwonBW, LiuJ, MessererC, et al. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 2002; 99: 3246–51.
71. LieblDJ, HuangW, YoungW, et al. Regulation of Trk receptors following contusion of the rat spinal cord. Exp Neurol 2001; 167: 15–26.
72. LuP, BleschA, TuszynskiMH. Neurotrophism without neurotropism: BDNF promotes survival but not growth of lesioned corticospinal neurons. J Comp Neurol 2001; 436: 456–70.
73. KingVR, BradburyEJ, McMahonSB, et al. Changes in truncated trkB and p75 receptor expression in the rat spinal cord following spinal cord hemisection and spinal cord hemisection plus neurotrophin treatment. Exp Neurol 2000; 165: 327–41.
74. GarrawaySM, AndersonAJ, MendellLM. BDNF-induced facilitation of afferent-evoked responses in lamina II neurons is reduced after neonatal spinal cord contusion injury. J Neurophysiol 2005; 94: 1798–804.
75. DoughertyKD, DreyfusCF, BlackIB. Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiol Dis 2000; 7: 574–85.
76. CoullJA, BeggsS, BoudreauD, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438: 1017–21.
77. BoulenguezP, LiabeufS, BosR, et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med 2011; 16: 302–7.
78. von MeyenburgJ, BrosamleC, MetzGAS, et al. Regeneration and sprouting of chronically injured corticospinal tract fibers in adult rats promoted by NT-3 and the mAb IN-1, which neutralizes myelin-associated neurite growth inhibitors. Exp Neurol 1998; 154: 583–94.
79. GrillRA, BleschA, TuszynskiMH. Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells. Exp Neurol 1997; 148: 444–52.
80. CoumansJV, LinT T-S, DaiHN, et al. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci 2001; 21: 9334–44.
81. YeJH, HouleJD. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol 1997; 143: 70–81.
82. GonzalezM, CollinsWF III. Modulation of motoneuron excitability by brain-derived neurotrophic factor. J Neurophysiol 1997; 77: 502–6.
83. JakemanLB, WeiP, GuanZ, et al. Brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury. Exp Neurol 1998; 154: 170–84.
84. XuXM, GuénardV, KleitmanN, et al. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat throracic spinal cord. Exp Neurol 1995; 134: 261–72.
85. ArvanianVL, HornerPJ, GageFH, et al. Intrathecal neurotrophin-3-secreting fibroblasts strengthen synaptic connections to motoneurons in the neonatal rat. J Neurosci 2003; 23: 8706–12.
86. ArvanianVL, BowersWJ, AndersonAJ, et al. Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat. Exp Neurol 2006; 197: 347–52.
87. BoyceVS, TumoloM, FischerI, et al. Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. J Neurophysiol 2007; 98: 1988–96.
88. BleschA, LuP, TuszynskiMHNeurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 2002; 57: 833–8.
89. LiuY, HimesBT, SolowskaJ, et al. Intraspinal delivery of neurotrophin-3 using neural stem cells genetically modified by recombinant retrovirus. Exp Neurol 1999; 158: 9–26.
90. BlitsB, OudegaM, BoerGJ, et al. Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function. Neuroscience 2003; 118: 271–81.
91. Boyce, VS, Park, J, Gage, FH, et al. Differential effects of BDNF and NT-3 on hindlimb function in paraplegic rats. Eur J Neurosci 2012; 53: 221–32.
92. FortunJ, PuzisR, PearseDD, et al. Muscle injection of AAV-NT-3 promotes anatomical reorganization of CST axons and improves behavioral outcome following SCI. J Neurotrauma 2009; 26: 941–53.
93. PetruskaJC, KitayB, BoyceVS, et al. Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult rats. Eur J Neurosci 2010; 32: 997–1005.
94. BlitsB, DijkhuizenPA, BoerGJ, et al. Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injured rat corticospinal tract fibers and improve hindlimb function. Exp Neurol 2000; 164: 25–37.
95. EdgertonVR, CourtineG, GerasimenkoYP, et al. Training locomotor networks. Brain Res Rev 2008; 57: 241–54.
96. CourtineG, GerasimenkoY, van den BrandR, et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci 2009; 12: 1333–42.
97. CôtéMP, AzzamGA, LemayMA, et al. Activity-dependent increase in neurotrophic factors is associated with an enhanced modulation of spinal reflexes after spinal cord injury. J Neurotrauma 2011; 28: 299–309.
98. YingZ, RoyRR, EdgertonVR, et al. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol 2005; 193: 411–19.
99. AngET, Gomez-PinillaF. Potential therapeutic effects of exercise to the brain. Curr Med Chem 2007; 14: 2564–71.
100. PetruskaJC, IchiyamaRM, CrownED, et al. Changes in motoneuron properties and synaptic inputs related to step training following spinal cord transection in rats. J Neurosci 2007; 27: 4460–71.
101. YingZ., RoyRR, ZhongH, et al. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuroscience 2008; 155: 1070–8.
102. ArvanovVL, SeebachBS, Mendell LM NT-3 evokes an LTP- like facilitation of AMPA/Kainate-mediated synaptic transmission in the neonatal rat spinal cord. J Neurophysiol 2000; 84: 752–8.
103. ArvanianVL, BowersWJ, PetruskaJC, et al. Viral delivery of NR2D subunits reduces Mg2+ block of NMDA receptor and restores NT-3-induced potentiation of AMPA/kainate responses in maturing rat motoneuronsJ Neurophysiol 2004; 92: 2394–404.
104. SchnellL, HunanyanA, BowersW, et al. Combined delivery of Nogo-A antibody, neurotrophin-3 and NMDA-2D subunits establishes a functional “detour” in a hemisected spinal cord. Eur J Neurosci 2011; 34: 1256–67.
105. García-AlíasG, PetrosyanH, SchnellH, et al. Chondroitinase ABC combined with NT3 secretion and NR2D expression promotes axonal plasticity and functional recovery in rats with lateral hemisection of the spinal cord. J Neurosci 2011; 31: 17788–99.
106. SchnellL, SchwabME. Sprouting and regeneration of lesioned corticospinal tract fibres in the adult rat spinal cord. Eur J Neurosci 1993; 5: 1156–71.
107. SchnellL, SchneiderR, KolbeckR, et al. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesions. Nature 1994; 367: 170–3.
108. TuszynskiMH, GrillR, JonesLL, et al. NT-3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves functional deficits after chronic scar resection. Exp Neurol 2003; 181: 47–56.
109. BamberNI, LiH, LuX, et al. Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels. Eur J Neurosci 2001; 3: 257–68.
110. ChenQ, SmithGM, ShineHD. Immune activation is required for NT-3-induced axonal plasticity in chronic spinal cord injury. Exp Neurol 2008; 209: 497–509.
111. VavrekR, GirgisJ, TetzlaffW, et al. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain 2006; 129: 1534–45.
112. HaggT, BakerKA, EmsleyJG, et al. Prolonged local neurotrophin-3 infusion reduces ipsilateral collateral sprouting of spared corticospinal axons in adult rats. Neuroscience 2005; 130: 875–87.
113. JinY, TesslerA, FischerI, et al. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp Neurol 2002; 177: 265–75.
114. MeneiP, Montero-MeneiC, WhittemoreSR, et al. Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J Neurosci 1998; 10: 607–21.
115. BregmanBS, McAteeM, DaiHN, et al. Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp Neurol 1997; 148: 475–94.
116. TobiasCA, ShumskyJS, ShibataM, et al. Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration. Exp Neurol 2003; 184: 97–113.
117. LawrenceDG, KuypersHG. The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. Brain 1968; 91: 1–14.
118. LawrenceDG, KuypersHG. The functional organization of the motor system in the monkey. II. The effects of lesions of the descending brain-stem pathways. Brain 1968; 91: 15–36.

References

1. AguayoAJ, RasminskyM, BrayGM, et al. Degenerative and regenerative responses of injured neurons in the central nervous system of adult mammals. Philos Trans R Soc Lond B Biol Sci 1991; 331: 337–43.
2. DavidS, AguayoAJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 1981; 214: 931–3.
3. RichardsonPM, McGuinnessUM, AguayoAJ. Axons from CNS neurons regenerate into PNS grafts. Nature 1980; 284: 264–5.
4. YiuG, HeZ. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 2006; 7: 617–27.
5. BradburyEJ, MoonLDF, PopatRJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416: 636–40.
6. LeeJK, GeoffroyCG, ChanAF, et al. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 2010; 66: 663–70.
7. LeeJK, ChowR, XieF, et al. Combined genetic attenuation of myelin and semaphorin-mediated growth inhibition is insufficient to promote serotonergic axon regeneration. J Neurosci 2010; 30: 10899–904.
8. ParkKK, LiuK, HuY, et al. PTEN/mTOR and axon regeneration. Exp Neurol 2010; 223: 45–50.
9. BregmanBS, Kunkel-BagdenE, ReierPJ, et al. Recovery of function after spinal cord injury: mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats. Exp Neurol 1993; 123: 3–16.
10. HowlandDR, BregmanBS, TesslerA, et al. Transplants enhance locomotion in neonatal kittens whose spinal cords are transected: a behavioral and anatomical study. Exp Neurol 1995; 135: 123–45.
11. ChenDF, JhaveriS, SchneiderGE. Intrinsic changes in developing retinal neurons result in regenerative failure of their axons. Proc Natl Acad Sci U S A 1995; 92: 7287–91.
12. LiD, FieldPM, RaismanG. Failure of axon regeneration in postnatal rat entorhinohippocampal slice coculture is due to maturation of the axon, not that of the pathway or target. Eur J Neurosci 1995; 7: 1164–71.
13. BlackmoreM, LetourneauPC. Changes within maturing neurons limit axonal regeneration in the developing spinal cord. J Neurobiol 2006; 66: 348–60.
14. GoldbergJL, KlassenMP, HuaY, et al. Amacrine signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 2002; 296: 1860–4.
15. HallDE, NeugebauerKM, ReichardtLF. Embryonic neural retinal cell response to extracellular matrix proteins: developmental changes and effects of the cell substratum attachment antibody (CSAT). J Cell Biol 1987; 104: 623–34.
16. MooreDL, BlackmoreMG, HuY, et al. KLF family members regulate intrinsic axon regeneration ability. Science 2009; 326: 298–301.
17. McConnellBB, YangVW. Mammalian Krüppel-like factors in health and diseases. Physiol Rev 2010; 90: 1337–81.
18. VeldmanMB, BembenMA, ThompsonRC, et al. Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration. Dev Biol 2007; 312: 596–612.
19. VeldmanMB, BembenMA, GoldmanD. Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish. Mol Cell Neurosci 2010; 43: 370–83.
20. JacobsAJ, SwainGP, SnedekerJA, et al. Recovery of neurofilament expression selectively in regenerating reticulospinal neurons. J Neurosci 1997; 17: 5206–20.
21. BeckerT, BernhardtRR, ReinhardE, et al. Readiness of zebrafish brain neurons to regenerate a spinal axon correlates with differential expression of specific cell recognition molecules. J Neurosci 1998; 18: 5789–803.
22. AndersonPN, CampbellG, ZhangY, LiebermanAR. Cellular and molecular correlates of the regeneration of adult mammalian CNS axons into peripheral nerve grafts. Prog Brain Res 1998; 117: 211–32.
23. Vidal-SanzM, BrayGM, Villegas-PérezMP, et al. Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J Neurosci 1987; 7: 2894–909.
24. Villegas-PérezMP, Vidal-SanzM, BrayGM, et al. Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. J Neurosci 1988; 8: 265.
25. CoumansJV, LinTT, DaiHN, et al. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci 2001; 21: 9334–44.
26. MartiniR, SchachnerM. Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and myelin-associated glycoprotein) in regenerating adult mouse sciatic nerve. J Cell Biol 1988; 106: 1735–46.
27. ShibuyaY, MizoguchiA, TakeichiM, et al. Localization of N-cadherin in the normal and regenerating nerve fibers of the chicken peripheral nervous system. Neuroscience 1995; 67: 253–61.
28. ThorntonMR, MantovaniC, BirchallMA, et al. Quantification of N-CAM and N-cadherin expression in axotomized and crushed rat sciatic nerve. J Anat 2005; 206: 69–78.
29. BatesCA, BeckerCG, MiotkeJA, et al. Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro. Exp Neurol 1999; 155: 128–39.
30. ChaisuksuntV, ZhangY, AndersonPN, et al. Axonal regeneration from CNS neurons in the cerebellum and brainstem of adult rats: correlation with the patterns of expression and distribution of messenger RNAs for L1, CHL1, cjun and growth-associated protein-43. Neuroscience 2000; 100: 87–108.
31. BeckerCG, LieberothBC, MorelliniF, et al. L1.1 is involved in spinal cord regeneration in adult zebrafish. J Neurosci 2004; 24: 7837–42.
32. ZhangY, BoX, SchoepferR, et al. Growth-associated protein GAP-43 and L1 act synergistically to promote regenerative growth of Purkinje cell axons in vivo. Proc Natl Acad Sci U S A 2005; 102: 14883–8.
33. ChenJ, WuJ, ApostolovaI, et al. Adeno-associated virus-mediated L1 expression promotes functional recovery after spinal cord injury. Brain 2007; 130: 954–69.
34. RoonprapuntC, HuangW, GrillR, et al. Soluble cell adhesion molecule L1-Fc promotes locomotor recovery in rats after spinal cord injury. J Neurotrauma 2003; 20: 871–82.
35. HallGF, PoulosA, CohenMJ. Sprouts emerging from the dendrites of axotomized lamprey central neurons have axonlike ultrastructure. J Neurosci 1989; 9: 588–99.
36. MacklerSA, YinHS, SelzerME. Determinants of directional specificity in the regeneration of lamprey spinal axons. J Neurosci 1986; 6: 1814–21.
37. ChoEY, SoKF. De novo formation of axon-like processes from axotomized retinal ganglion cells which exhibit long distance growth in a peripheral nerve graft in adult hamsters. Brain Res 1989; 484: 371–7.
38. Villegas-PérezMP, Vidal-SanzM, RasminskyM, et al. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J Neurobiol 1993; 24: 23–36.
39. LauKC, SoKF, TayD. Intravitreal transplantation of a segment of peripheral nerve enhances axonal regeneration of retinal ganglion cells following distal axotomy. Exp Neurol 1994; 128: 211–5.
40. DosterSK, LozanoAM, AguayoAJ, et al. Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury. Neuron 1991; 6: 635–47.
41. HaggT, Fass-HolmesB, VahlsingHL, et al. Nerve growth factor (NGF) reverses axotomy-induced decreases in choline acetyltransferase, NGF receptor and size of medial septum cholinergic neurons. Brain Res 1989; 505: 29–38.
42. KwonBK, LiuJ, MessererC, et al. Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 2002; 99: 3246–51.
43. ShifmanMI, ZhangG, SelzerME. Delayed death of identified reticulospinal neurons after spinal cord injury in lampreys. J Comp Neurol 2008; 510: 269–82.
44. ShifmanMI, SelzerME. Expression of the netrin receptor UNC-5 in lamprey brain: modulation by spinal cord transection. Neurorehabil Neural Repair 2000; 14: 49–58.
45. ShifmanMI, YumulRE, LaramoreC, et al. Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey. Exp Neurol 2009; 217: 242–51.
46. MatsunagaE, Tauszig-DelamasureS, MonnierPP, et al. RGM and its receptor neogenin regulate neuronal survival. Nat Cell Biol 2004; 6: 749–55.
47. MehlenP, MazelinL. The dependence receptors DCC and UNC5H as a link between neuronal guidance and survival. Biol Cell 2003; 95: 425–36.
48. InoueT, HosokawaM, MorigiwaK, et al. Bcl-2 overexpression does not enhance in vivo axonal regeneration of retinal ganglion cells after peripheral nerve transplantation in adult mice. J Neurosci 2002; 22: 4468–77.
49. ZivNE, SpiraME. Localized and transient elevations of intracellular Ca2+ induce the dedifferentiation of axonal segments into growth cones. J Neurosci 1997; 17: 3568–79.
50. MandolesiG, MadedduF, BozziY, et al. Acute physiological response of mammalian central neurons to axotomy: ionic regulation and electrical activity. FASEB J 2004; 18: 1934–6.
51. Ghosh-RoyA, WuZ, GoncharovA, et al. Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J Neurosci 2010; 30: 3175–83.
52. HammarlundM, NixP, HauthL, et al. Axon regeneration requires a conserved MAP kinase pathway. Science 2009; 323: 802–6.
53. XiongX, WangX, EwanekR, et al. Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J Cell Biol 2010; 191: 211–23.
54. ItohA, HoriuchiM, BannermanP, et al. Impaired regenerative response of primary sensory neurons in ZPK/DLK gene-trap mice. Biochem Biophys Res Commun 2009; 383: 258–62.
55. HanzS, PerlsonE, WillisD, et al. Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 2003; 40: 1095–104.
56. PerlsonE, HanzS, Ben-YaakovK, et al. Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve. Neuron 2005; 45: 715–26.
57. LaiK, ZhaoY, Ch’ngTH, et al. Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proc Natl Acad Sci U S A 2008; 105: 17175–80.
58. YudinD, HanzS, YooS, et al. Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve. Neuron 2008; 59: 241–52.
59. OkuyamaN, Kiryu-SeoS, KiyamaH. Altered expression of Smad family members in injured motor neurons of rat. Brain Res 2007; 1132: 36–41.
60. ZouH, HoC, WongK, et al. Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons. J Neurosci 2009; 29: 7116–23.
61. CavalliV, KujalaP, KlumpermanJ, et al. Sunday Driver links axonal transport to damage signaling. J Cell Biol 2005; 168: 775–87.
62. LindwallC, KanjeM. Retrograde axonal transport of JNK signaling molecules influence injury induced nuclear changes in p-c-Jun and ATF3 in adult rat sensory neurons. Mol Cell Neurosci 2005; 29: 269–82.
63. McQuarrieIG, GrafsteinB, GershonMD. Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP. Brain Res 1977; 132: 443–53.
64. NeumannS, WoolfCJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999; 23: 83–91.
65. QiuJ, CaiD, DaiH, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002; 34: 895–903.
66. CaoZ, GaoY, BrysonJB, et al. The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci 2006; 26: 5565–73.
67. Hyatt SachsH, RohrerH, ZigmondRE. The conditioning lesion effect on sympathetic neurite outgrowth is dependent on gp130 cytokines. Exp Neurol 2010; 223: 516–22.
68. McQuarrieIG, JacobJM. Conditioning nerve crush accelerates cytoskeletal protein transport in sprouts that form after a subsequent crush. J Comp Neurol 1991; 305: 139–47.
69. McKerracherL, Vidal-SanzM, AguayoAJ. Slow transport rates of cytoskeletal proteins change during regeneration of axotomized retinal neurons in adult rats. J Neurosci 1990; 10: 641–8.
70. McKerracherL, Vidal-SanzM, EssagianC, et al. Selective impairment of slow axonal transport after optic nerve injury in adult rats. J Neurosci 1990; 10: 2834–41.
71. LuX, RichardsonPM. Inflammation near the nerve cell body enhances axonal regeneration. J Neurosci 1991; 11: 972–8.
72. YinY, CuiQ, LiY, et al. Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci 2003; 23: 2284–93.
73. YinY, HenzlMT, LorberB, et al. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 2006; 9: 843–52.
74. YinY, CuiQ, GilbertH, et al. Oncomodulin links inflammation to optic nerve regeneration. Proc Natl Acad Sci U S A 2009; 106: 19587–92.
75. LeibingerM, MüllerA, AndreadakiA, et al. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci 2009; 29: 14334–41.
76. LeaverSG, CuiQ, PlantGW, et al. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells. Gene Ther 2006; 13: 1328–41.
77. MüllerA, HaukTG, LeibingerM et al. Exogenous CNTF stimulates axon regeneration of retinal ganglion cells partially via endogenous CNTF. Mol Cell Neurosci 2009; 41: 233–46.
78. LundePK, SejerstedOM. Intracellular calcium signalling in striated muscle cells. Scand J Clin Lab Invest 1997; 57: 559–68.
79. NarazakiM, FujimotoM, MatsumotoT, et al. Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling. Proc Natl Acad Sci U S A 1998; 95: 13130–4.
80. SmithPD, SunF, ParkKK, et al. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 2009; 64: 617–23.
81. HellströmM, MuhlingJ, EhlertEM, et al. Negative impact of rAAV2 mediated expression of SOCS3 on the regeneration of adult retinal ganglion cell axons. Mol Cell Neurosci 2010; 46: 507–15.
82. MiaoT, WuD, ZhangY, et al. Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons. J Neurosci 2006; 26: 9512–19.
83. HornKP, BuschSA, HawthorneAL, et al. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 2008; 28: 9330–41.
84. PopovichPG, GuanZ, WeiP, et al. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol 1999; 158: 351–65.
85. BetheaJR, DietrichWD. Targeting the host inflammatory response in traumatic spinal cord injury. Curr Opin Neurol 2002; 15: 355–60.
86. NeumannH, SchweigreiterR, YamashitaT, et al. Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism. J Neurosci 2002; 22: 854–62.
87. BabcockAA, KuzielWA, RivestS,et al. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci 2003; 23: 7922–30.
88. BitoH, FuruyashikiT, IshiharaH, et al. A critical role for a Rhoassociated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons. Neuron 2000; 26: 431–41.
89. LehmannM, FournierA, Selles-NavarroI, et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 1999; 19: 7537–47.
90. TigyiG, FischerDJ, SebokA, et al. Lysophosphatidic acid-induced neurite retraction in PC12 cells: control by phosphoinositide–Ca+2 signaling and Rho. J Neurochem 1996; 66: 537–48.
91. DemjenD, KlussmannS, KleberS, et al. Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury. Nat Med 2004; 10: 389–95.
92. GrisD, MarshDR, OatwayMA, et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci 2004; 24: 4043–51.
93. GonzalezR, GlaserJ, LiuMT, et al. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp Neurol 2003; 184: 456–63.
94. MarkusA, PatelTD, SniderWD. Neurotrophic factors and axonal growth. Curr Opin Neurobiol 2002; 12: 523–31.
95. SchnellL, SchneiderR, KolbeckR, et al. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 1994; 367: 170–3.
96. RamerMS, PriestleyJV, McMahonSB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312–16.
97. WangR, KingT, OssipovMH, et al. Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury. Nat Neurosci 2008; 11: 488–96.
98. HarveyP, GongB, RossomandoAJ, et al. Topographically specific regeneration of sensory axons in the spinal cord. Proc Natl Acad Sci U S A 2010; 107: 11585–90.
99. LiuY, KimD, HimesBT, et al. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci 1999; 19: 4370–87.
100. BleschA, TuszynskiMH. Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells. Exp Neurol 1997; 148: 444–52.
101. CaiD, ShenY, De BellardM, et al. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 1999; 22: 89–101.
102. McKerracherL, DavidS, JacksonDL, et al. Identification of myelin-associated glycoprotein as a major myelinderived inhibitor of neurite growth. Neuron 1994; 13: 805–11.
103. MukhopadhyayG, DohertyP, WalshFS, et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994; 13: 757–67.
104. ChenMS, HuberAB, van der HaarME, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434–9.
105. GrandPréT, NakamuraF, VartanianT, et al. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000; 403: 439–44.
106. PrinjhaR, MooreSE, VinsonM, et al. Inhibitor of neurite outgrowth in humans. Nature 2000; 403: 383–4.
107. KottisV, ThibaultP, MikolD, et al. Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J Neurochem 2002; 82: 1566–9.
108. WangKC, KoprivicaV, KimJA, et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 2002; 417: 941–4.
109. DomeniconiM, CaoZ, SpencerT, et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 2002; 35: 283–90.
110. FournierAE, GrandPreT, StrittmatterSM. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409: 341–6.
111. HouS, TianW, XuQ, et al. The enhancement of cell adherence and inducement of neurite outgrowth of dorsal root ganglia co-cultured with hyaluronic acid hydrogels modified with Nogo-66 receptor antagonist in vitro. Neuroscience 2006; 137: 519–29.
112. AtwalJK, Pinkston-GosseJ, SykenJ, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 2008; 322: 967–70.
113. VenkateshK, ChivatakarnO, LeeH, et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin associated glycoprotein. J Neurosci 2005; 25: 808–22.
114. CaiD, QiuJ, CaoZ, et al. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 2001; 21: 4731–9.
115. ZhengB, AtwalJ, HoC, et al. Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc Natl Acad Sci U S A 2005; 102: 1205–10.
116. ZörnerB, SchwabME. Anti-Nogo on the go: from animal models to a clinical trial. Ann N Y Acad Sci 2010; 1198: E22–34.
117. DaviesSJ, GoucherDR, DollerC, et al. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 1999; 19: 5810–22.
118. McKeonRJ, SchreiberRC, RudgeJS, et al. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 1991; 11: 3398–411.
119. RollsA, ShechterR, SchwartzM. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 2009; 10: 235–41.
120. FawcettJW, AsherRA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49: 377–91.
121. GrimpeB, PressmanY, LupaMD, et al. The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Mol Cell Neurosci 2005; 28: 18–29.
122. SteinmetzMP, HornKP, TomVJ, et al. Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord. J Neurosci 2005; 25: 8066–76.
123. ZuoJ, FergusonTA, HernandezYJ, et al. Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan. J Neurosci 1998; 18: 5203–11.
124. ZuoJ, NeubauerD, GrahamJ, et al. Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp Neurol 2002; 176: 221–8.
125. ShenY, TenneyAP, BuschSA, et al. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 2009; 326: 592–6.
126. FryEJ, ChagnonMJ, López-ValesR, et al. Corticospinal tract regeneration after spinal cord injury in receptor protein tyrosine phosphatase sigma deficient mice. Glia 2010; 58: 423–33.
127. NiederostB, OertleT, FritscheJ, et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 2002; 22(23): 10368–76.
128. WintonMJ, DubreuilCI, LaskoD, et al. Characterization of new cell permeable C3-like proteins that inactivate Rho and stimulate neurite outgrowth on inhibitory substrates. J Biol Chem 2002; 277: 226570–7.
129. DerghamP, EllezamB, EssagianC, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22: 6570–7.
130. DubreuilCI, WintonMJ, McKerracherL. Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol 2003; 162: 233–43.
131. MaduraT, YamashitaT, KuboT, et al. Activation of Rho in the injured axons following spinal cord injury. EMBO Rep 2004; 5: 412–17.
132. SongH, MingG, HeZ, et al. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 1998; 281: 1515–18.
133. BandtlowC, ZachlederT, SchwabME. Oligodendrocytes arrest neurite growth by contact inhibition. J Neurosci 1990; 10: 3837–48.
134. FawcettJW, RokosJ, BakstI. Oligodendrocytes repel axons and cause axonal growth cone collapse. J Cell Sci 1989; 92: 93–100.
135. LiJ, YenC, LiawD, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943–7.
136. NingK, DrepperC, ValoriCF, et al. PTEN depletion rescues axonal growth defect and improves survival in SMNdeficient motor neurons. Hum Mol Genet 2010; 19: 3159–68.
137. LiuK, LuY, LeeJK, et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010; 13: 1075–81.
138. ParkKK, LiuK, HuY, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008; 322: 963–6.
139. ChristieKJ, WebberCA, MartinezJA, et al. PTEN inhibition to facilitate intrinsic regenerative outgrowth of adult peripheral axons. J Neurosci 2010; 30: 9306–15.
140. KurimotoT, YinY, OmuraK, et al. Long-distance axon regeneration in the mature optic nerve: contributions of oncomodulin, cAMP, and pten gene deletion. J Neurosci 2010; 30: 15654–63.
141. ArevaloM, Rodríguez-TébarA. Activation of casein kinase II and inhibition of phosphatase and tensin homologue deleted on chromosome 10 phosphatase by nerve growth factor/p75NTR inhibit glycogen synthase kinase-3beta and stimulate axonal growth. Mol Biol Cell 2006; 17: 3369–77.
142. ZhouF, ZhouJ, DedharS, et al. NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. Neuron 2004; 42: 897–912.
143. YoshimuraT, KawanoY, ArimuraN, et al. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 2005; 120: 137–49.
144. JiangH, GuoW, LiangX, et al. Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators. Cell 2005; 120: 123–35.
145. ZhouF, SniderWD. Intracellular control of developmental and regenerative axon growth. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1575–92.
146. ZhouF, WalzerM, WuY, et al. Neurotrophins support regenerative axon assembly over CSPGs by an ECMintegrin-independent mechanism. J Cell Sci 2006; 119: 2787–96.
147. DillJ, WangH, ZhouF, et al. Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J Neurosci 2008; 28: 8914–28.
148. AlabedYZ, PoolM, Ong ToneS, et al. GSK3 beta regulates myelin-dependent axon outgrowth inhibition through CRMP4. J Neurosci 2010; 30: 5635–43.
149. MingGL, SongHJ, BerningerB, et al. cAMP-dependent growth cone guidance by netrin-1. Neuron 1997; 19: 1225–35.
150. NishiyamaM, HoshinoA, TsaiL, et al. Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning. Nature 2003; 424: 990–5.
151. PearseDD, PereiraFC, MarcilloAE, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med 2004; 10: 610–16.
152. BhattDH, OttoSJ, DepoisterB, et al. Cyclic AMP induced repair of zebrafish spinal circuits. Science 2004; 305: 254–8.
153. NikulinaE, TidwellJL, DaiHN, et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 2004; 101: 8786–90.
154. UdinaE, LadakA, FureyM, et al. Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration. Exp Neurol 2010; 223: 143–52.
155. JinL, ZhangG, JamisonC, et al. Axon regeneration in the absence of growth cones: acceleration by cyclic AMP. J Comp Neurol 2009; 515: 295–312.
156. ParkKK, HuY, MuhlingJ, et al. Cytokine-induced SOCS expression is inhibited by cAMP analogue: impact on regeneration in injured retina. Mol Cell Neurosci 2009; 41: 313–24.
157. LuP, YangH, JonesLL, et al. Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J Neurosci 2004; 24: 6402–9.
158. KadoyaK, TsukadaS, LuP, et al. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 2009; 64: 165–72.
159. JinZ, StrittmatterSM. Rac1 mediates collapsin-1-induced growth cone collapse. J Neurosci 1997; 17: 6256–63.
160. BorisoffJF, ChanCC, HiebertGW, et al. Suppression of Rhokinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 2003; 22: 405–16.
161. MonnierPP, SierraA, SchwabJM, et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 2003; 22: 319–30.
162. ShearerMC, NiclouSP, BrownD, et al. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways. Mol Cell Neurosci 2003; 24: 913–25.
163. WahlS, BarthH, CiossekT, et al. Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J Cell Biol 2000; 149: 263–70.
164. LiZ, DongX, DongX, et al. Regulation of PTEN by Rho small GTPases. Nat Cell Biol 2005; 7: 399–404.
165. FournierAE, TakizawaBT, StrittmatterSM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci 2003; 23: 1416–23.
166. FehlingsMG, TheodoreN, HarropJ, et al. A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma 2011; 28: 787–96.
167. SengottuvelV, LeibingerM, PfreimerM, et al. Taxol facilitates axon regeneration in the mature CNS. J Neurosci 2011; 31: 2688–99.
168. SchwaigerFW, HagerG, SchmittAB, et al. Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT). Eur J Neurosci 2000; 12: 1165–76.
169. QiuJ, CaffertyWBJ, McMahonSB, et al. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci 2005; 25: 1645–53.
170. BareyreFM, GarzorzN, LangC, et al. In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration. Proc Natl Acad Sci U S A 2011; 108: 6282–7.
171. SmithRP, Lerch-HanerJK, PardinasJR, et al. Transcriptional profiling of intrinsic PNS factors in the postnatal mouse. Mol Cell Neurosci 2011; 46: 32–44.
172. MacGillavryHD, StamFJ, SassenMM, et al. NFIL3 and cAMP response element-binding protein form a transcriptional feedforward loop that controls neuronal regeneration-associated gene expression. J Neurosci 2009; 29: 15542–50.
173. MacGillavryHD, CornelisJ, van der KallenLR, et al. Genome-wide gene expression and promoter binding analysis identifies NFIL3 as a repressor of C/EBP target genes in neuronal outgrowth. Mol Cell Neurosci 2011; 46: 460–8.
174. RaivichG, BohatschekM, Da CostaC, et al. The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 2004; 43: 57–67.
175. TsujinoH, KondoE, FukuokaT, et al. Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury. Mol Cell Neurosci 2000; 15: 170–82.
176. MasonMRJ, LiebermanAR, AndersonPN. orticospinal neurons up-regulate a range of growth-associated genes following intracortical, but not spinal, axotomy. Eur J Neurosci 2003; 18: 789–802.
177. ChaisuksuntV, CampbellG, ZhangY, et al. Expression of regeneration-related molecules in injured and regenerating striatal and nigral neurons. J Neurocytol 2003; 32: 161–83.
178. SaulKE, KokeJR, GarcíaDM. Activating transcription factor 3 (ATF3) expression in the neural retina and optic nerve of zebrafish during optic nerve regeneration. Comp Biochem Physiol A 2010; 155: 172–82.
179. SeijffersR, MillsCD, WoolfCJ. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J Neurosci 2007; 27: 7911–20.
180. GomezTM, RoblesE, PooM, et al. Filopodial calcium transients promote substrate-dependent growth cone turning. Science 2001; 291: 1983–7.
181. NishiyamaM, Schimmelmann vonMJ, TogashiK, et al. Membrane potential shifts caused by diffusible guidance signals direct growth-cone turning. Nat Neurosci 2008; 11: 762–71.
182. JacobJM, McQuarrieIG. Axotomy accelerates slow component b of axonal transport. J Neurobiol 1991; 22: 570–82.
183. ValeRD, ReeseTS, SheetzMP. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 1985; 42: 39–50.
184. YildizA, TomishigeM, ValeRD, et al. Kinesin walks hand-over-hand. Science 2004; 303: 676–8.
185. ValeRD. The molecular motor toolbox for intracellular transport. Cell 2003; 112: 467–80.
186. BrownA. Axonal transport of membranous and nonmembranous cargoes: a unified perspective. J Cell Biol 2003; 160: 817–21.
187. RoyS, CoffeeP, SmithG, et al. Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. J Neurosci 2000; 20: 6849–61.
188. SchnappBJ, ReeseTS. Dynein is the motor for retrograde axonal transport of organelles. Proc Natl Acad Sci U S A 1989; 86: 1548–52.
189. LaMonteBH, WallaceKE, HollowayBA, et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 2002; 34: 715–27.
190. RochlinMW, WicklineKM, BridgmanPC. Microtubule stability decreases axon elongation but not axoplasm production. J Neurosci 1996; 16: 3236–46.
191. KleitmanN, JohnsonMI. Rapid growth cone translocation on laminin is supported by lamellipodial not filopodial structures. Cell Motil Cytoskeleton 1989; 13: 288–300.
192. BentleyD, O’ConnorTP. Cytoskeletal events in growth cone steering. Curr Opin Neurobiol 1994; 4: 43–8.
193. ZhouFQ, CohanCS. How actin filaments and microtubules steer growth cones to their targets. J Neurobiol 2004; 58: 84–91.
194. ErtürkA, HellalF, EnesJ, et al. Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration. J Neurosci 2007; 27: 9169–80.
195. TetzlaffW, AlexanderSW, MillerFD, et al. Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci 1991; 11: 2528–44.
196. LurieDI, PijakDS, SelzerME. Structure of reticulospinal axon growth cones and their cellular environment during regeneration in the lamprey spinal cord. J Comp Neurol 1994; 344: 559–80.
197. PijakDS, HallGF, TenickiPJ, et al. Neurofilament spacing, phosphorylation, and axon diameter in regenerating and uninjured lamprey axons. J Comp Neurol 1996; 368: 569–81.
198. HallGF, YaoJ, SelzerME, et al. Cytoskeletal changes correlated with the loss of neuronal polarity in axotomized lamprey central neurons. J Neurocytol 1997; 26: 733–53.
199. CheeverTR, OlsonEA, ErvastiJM. Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-Actin in vivo. PLoS One 2011; 6: e17768.
200. LannersHN, GrafsteinB. Early stages of axonal regeneration in the goldfish optic tract: an electron microscopic study. J Neurocytol 1980; 9: 733–51.
201. TesserP, JonesPS, SchechterN. Elevated levels of retinal neurofilament mRNA accompany optic nerve regeneration. J Neurochem 1986; 47: 1235–43.
202. MarshL, LetourneauPC. Growth of neurites without filopodial or lamellipodial activity in the presence of cytochalasin B. J Cell Biol 1984; 99: 2041–7.
203. JonesSL, SelzerME, GalloG. Developmental regulation of sensory axon regeneration in the absence of growth cones. J Neurobiol 2006; 66: 1630–45.
204. NordlanderRH. Axonal growth cones in the developing amphibian spinal cord. J Comp Neurol 1987; 263: 485–96.
205. HellalF, HurtadoA, RuschelJ, et al. Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury. Science 2011; 331: 928–31.
206. StiessM, MaghelliN, KapiteinLC, et al. Axon extension occurs independently of centrosomal microtubule nucleation. Science 2010; 327: 704–7.
207. WillisDE, TwissJL. Profiling axonal mRNA transport. Methods Mol Biol 2011; 714: 335–52.
208. GioioAE, LavinaZS, JurkovicovaD, et al. Nerve terminals of squid photoreceptor neurons contain a heterogeneous population of mRNAs and translate a transfected reporter mRNA. Eur J Neurosci 2004; 20: 865–72.
209. ZivrajKH, TungYCL, PiperM, et al. Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. J Neurosci 2010; 30: 15464–78.
210. EdstromJE, EichnerD, EdstromA. The ribonucleic acid of axons and myelin sheaths from Mauthner neurons. Biochim Biophys Acta 1962; 61: 178–84.
211. KoenigE. Synthetic mechanisms in the axon. I. Local axonal synthesis of acetylcholinesterase. J Neurochem 1965; 12: 343–55.
212. KoenigE. Synthetic mechanisms in the axon. II. RNA in myelin-free axons of the cat. J Neurochem 1965; 12: 357–61.
213. CapanoCP, GiudittaA, CastigliE, et al. Occurrence and sequence complexity of polyadenylated RNA in squid axoplasm. J Neurochem 1987; 49: 698–704.
214. GiudittaA, MenichiniE, Perrone CapanoC, et al. Active polysomes in the axoplasm of the squid giant axon. J Neurosci Res 1991; 28: 18–28.
215. BassellGJ, ZhangH, ByrdAL, et al. Sorting of beta-actin mRNA and protein to neurites and growth cones in culture. J Neurosci 1998; 18: 251–65.
216. EngH, LundK, CampenotRB. Synthesis of beta-tubulin, actin, and other proteins in axons of sympathetic neurons in compartmented cultures. J Neurosci 1999; 19: 1–9.
217. KaplanBB, GioioAE, CapanoCP, et al. beta-Actin and beta-Tubulin are components of a heterogeneous mRNA population present in the squid giant axon. Mol Cell Neurosci 1992; 3: 133–44.
218. LeeS, HollenbeckPJ. Organization and translation of mRNA in sympathetic axons. J Cell Sci 2003; 116: 4467–78.
219. Olink-CouxM, HollenbeckPJ. Localization and active transport of mRNA in axons of sympathetic neurons in culture. J Neurosci 1996; 16: 1346–58.
220. GioioAE, ChunJT, CrispinoM, et al. Kinesin mRNA is present in the squid giant axon. J Neurochem 1994; 63: 13–18.
221. DavisL, DouP, DeWitM, et al. Protein synthesis within neuronal growth cones. J Neurosci 1992; 12: 4867–77.
222. van-MinnenJ. Axonal localization of neuropeptide-encoding mRNA in identified neurons of the snail Lymnaea stagnalis. Cell Tissue Res 1994; 276: 155–61.
223. ZhengJQ, KellyTK, ChangB, et al. A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons. J Neurosci 2001; 21: 9291–303.
224. WillisD, LiKW, ZhengJQ, et al. Differential transport and local translation of cytoskeletal, injury-response, and neurodegeneration protein mRNAs in axons. J Neurosci 2005; 25: 778–91.
225. KnowlesRB, SabryJH, MartoneME, et al. Translocation of RNA granules in living neurons. J Neurosci 1996; 16: 7812–20.
226. HengstU, JaffreySR. Function and translational regulation of mRNA in developing axons. Semin Cell Dev Biol 2007; 18: 209–15.
227. CampbellDS, HoltCE. Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation. Neuron 2001; 32: 1013–26.
228. MingG, WongST, HenleyJ, et al. Adaptation in the chemotactic guidance of nerve growth cones. Nature 2002; 417: 411–18.
229. WuKY, HengstU, CoxLJ, et al. Local translation of RhoA regulates growth cone collapse. Nature 2005; 436: 1020–4.
230. LeungK, van HorckFPG, LinAC, et al. Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. Nat Neurosci 2006; 9: 1247–56.
231. YaoJ, SasakiY, WenZ, et al. An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance. Nat Neurosci 2006; 9: 1265–73.
232. ZhangHL, EomT, OleynikovY, et al. Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron 2001; 31: 261–75.
233. ZhangHL, SingerRH, BassellGJ. Neurotrophin regulation of beta-actin mRNA and protein localization within growth cones. J Cell Biol 1999; 147: 59–70.
234. SmithDS, SkeneJH. A transcription-dependent switch controls competence of adult neurons for distinct modes of axon growth. J Neurosci 1997; 17: 646–58.
235. CostiganM, BefortK, KarchewskiL, et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 2002; 3: 16.
236. StamFJ, MacGillavryHD, ArmstrongNJ, et al. Identification of candidate transcriptional modulators involved in successful regeneration after nerve injury. Eur J Neurosci 2007; 25: 3629–37.
237. SkeneJH, WillardM. Characteristics of growth-associated polypeptides in regenerating toad retinal ganglion cell axons. J Neurosci 1981; 1: 419–26.
238. OestreicherAB, De GraanPN, GispenWH, et al. B-50, the growth associated protein-43: modulation of cell morphology and communication in the nervous system. Prog Neurobiol 1997; 53: 627–86.
239. AndersenLB, SchreyerDJ. Constitutive expression of GAP-43 correlates with rapid, but not slow regrowth of injured dorsal root axons in the adult rat. Exp Neurol 1999; 155: 157–64.
240. BuffoA, HoltmaatAJ, SavioT, et al. Targeted overexpression of the neurite growth-associated protein B- 59/GAP-43 in cerebellar Purkinje cells induces sprouting after axotomy but not axon regeneration into growth-permissive transplantsJ Neurosci 1997; 17: 8778–91.
241. MasonMR, CampbellG, CaroniP, et al. Overexpression of GAP-43 in thalamic projection neurons of transgenic mice does not enable them to regenerate axons through peripheral nerve grafts. Exp Neurol 2000; 165: 143–52.
242. BomzeHM, BulsaraKR, IskandarBJ, et al. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci 2001: 4: 38–43.
243. UdvadiaAJ, KosterRW, SkeneJH. GAP-43 promoter elements in transgenic zebrafish reveal a difference in signals for axon growth during CNS development and regeneration. Development 2001; 128: 1175–82.
244. NathanielEJ, PeaseDC. Regenerative changes in rat dorsal roots following Wallerian degeneration. J Ultrastruct Res 1963; 52: 533–49.
245. SchererSS, EasterSS. Degenerative and regenerative changes in the trochlear nerve of goldfish. J Neurocytol 1984; 13: 519–65.
246. BuschSA, HornKP, CuascutFX, et al. Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury. J Neurosci 2010; 30: 255–65.
247. BixbyJL, LilienJ, ReichardtLF. Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J Cell Biol 1988; 107: 353–61.
248. KleitmanN, SimonDK, SchachnerM, et al. Growth of embryonic retinal neurites elicited by contact with Schwann cell surfaces is blocked by antibodies to L1. Exp Neurol 1988; 102: 298–306.
249. SeilheimerB, SchachnerM. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture. J Cell Biol 1988; 107: 341–51.
250. WoodPM, SchachnerM, BungeRP. Inhibition of Schwann cell myelination in vitro by antibody to the L1 adhesion molecule. J Neurosci 1990; 10: 3635–45.
251. NeugebauerKM, TomaselliKJ, LilienJ, et al. Ncadherin, NCAM, and integrins promote retinal neurite outgrowth on astrocytes in vitro. J Cell Biol 1988; 107: 1177–87.
252. TomaselliKJ, NeugebauerKM, BixbyJL, et al. N-cadherin and integrins: two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces. Neuron 1988; 1: 33–43.
253. SunF, HeZ. Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol 2010; 20: 510–18.