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Comparisons between microvascular changes in cerebral and non-cerebral malaria in mice, using the retinal whole-mount technique

  • A. L. Neill (a1), T. Chan-Ling (a2) and N. H. Hunt (a2)

CBA/T6 mice inoculated with Plasmodium berghei ANKA strain (PbA) exhibited cerebral symptoms and died from cerebral malaria 6–8 days p.i. whereas DBA/2J mice developed (around days 6–9) a non-fatal cerebral malaria, with milder cerebral symptoms, and died between days 15 and 22 from other malaria-related complications. When inoculated with P. berghei K173 (Pb) these mouse strains did not develop cerebral malaria. These mouse/parasite strain combinations were used, in conjunction with the retinal whole-mount technique, to elucidate factors critical in the pathology of murine cerebral malaria. CBA/T6 mice infected with PbA (PbA-CBA mice) demonstrated mild changes in vascular permeability as early as days 2–3, prior to the appearance on day 5 of cerebral symptoms, whereas mice with non-cerebral malaria did not show any vascular permeability changes until the very late stage of the disease (days 14–22). In the PbA infections, progressive deterioration of endothelial barrier properties, demonstrated by Evans' Blue leakage both generally and from specific focal areas, as well as a developing monocytosis and adherence of mononuclear cells to the endothelium of the retinal vessels continued until death (in CBA/T6 mice) or resolution (in DBA/2J mice). Adherent monocytes, particularly in PbA-CBA mice, were associated with reduced Hoechst staining of individual endothelial cells and a banking up proximally of both parasitized and non-parasitized blood cells in the small blood vessels, often with accompanying focal leakage of Evans' Blue from the retinal vessels. The occurrence and severity of these early changes in the microcirculation correlated with the subsequent development of cerebral symptoms. Monocyte margination appeared to be the most significant factor associated with the development of cerebral symptoms.

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Aikawa, M., Iseki, M., Barnwell, J. W., Taylor, D., Oo, M. M. & Howard, R. J. (1990). The pathology of human cerebral malaria. American Journal of Tropical Medicine and Hygiene 43, 30–7.
Chan-Ling, T., Neill, A. L. & Hunt, N. H. (1992). Early microvascular changes in cerebral and non-cerebral malaria detected using retinal wholemounts. American Journal of Pathology 140, 1121–30.
Grau, G. E., Piguet, P.-F., Engers, H. D., Louis, J. A., Vassalli, P. & Lambert, P. H. (1986). L3T4+ lymphocytes play a major role in the pathogenesis of murine cerebral malaria. Journal of Immunology 137, 2348–54.
Grau, G. E., Fajardo, L. F., Piguet, P.-F., Allet, B., Lambert, P.-H. & Vassalli, P. (1987). Tumour necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–12.
Grau, G. E., Piguet, P.-F., Vassalli, P. & Lambert, P.-H. (1989). Tumour-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunology Reviews 112, 4970.
Hunt, N. H., Manduci, N. & Thumwood, C. M. (1993). Amelioration of murine cerebral malaria by dietary restriction. Parasitology 107, 471–6.
Neill, A. L. & Hunt, N. H. (1992). Pathology of fatal and resolving murine cerebral malaria. Parasitology 105, 165–75.
Rest, J. R. (1982). Cerebral malaria in inbred mice. I. A new model and its pathology. Transactions of the Royal Society for Tropical Medicine and Hygiene 76, 410–15.
Thumwood, C. M., Hunt, N. H., Clark, I. A. & Cowden, W. B. (1988). Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology 96, 579–89.
Thumwood, C. M., Hunt, N. H., Cowden, W. B. & Clark, I. A. (1989). Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. British Journal of Experimental Pathology 70, 293303.
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  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
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