Skip to main content
    • Aa
    • Aa

Effects of early low-level lead exposure on human brain structure, organization and functions

  • K. M. Cecil (a1)

Advanced neuroimaging techniques offer unique insights into how childhood lead exposure impacts the brain. Volumetric magnetic resonance imaging affords anatomical information about the size of global, regional and subcomponent structures within the brain. Diffusion tensor imaging provides information about white matter architecture by quantitatively describing how water molecules diffuse within it. Proton magnetic resonance spectroscopy generates quantitative measures of neuronal, axonal and glial elements via concentration levels of select metabolites. Functional magnetic resonance imaging infers neuronal activity associated with a given task performed. Employing these techniques in the study of the Cincinnati Lead Study, a relatively homogeneous birth cohort longitudinally monitored for over 30 years, one can non-invasively and quantitatively explore how childhood lead exposure is associated with adult brain structure, organization and function. These studies yield important findings how environmental lead exposure impacts human health.

Corresponding author
*Address for correspondence: K. M. Cecil, PhD, Professor, Radiology, Pediatrics, Neuroscience & Environmental Health, Cincinnati Children’s Hospital Medical Center, Department of Radiology, MLC 5033, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. (Email
Hide All
1.Al Khayat A, Menon NS, Alidina MR. Acute lead encephalopathy in early infancy – clinical presentation and outcome. Ann Trop Paediatr. 1997; 1, 3944.
2.Atre AL, Shinde PR, Shinde SN, et al. Pre- and posttreatment MR imaging findings in lead encephalopathy. AJNR Am J Neuroradiol. 2006; 27, 902903.
3.Mani J, Chaudhary N, Kanjalkar M, Shah PU. Cerebellar ataxia due to lead encephalopathy in an adult. J Neurol Neurosurg Psychiatr. 1998; 65, 797.
4.Tuzun M, Tuzun D, Salan A, Hekimoglu B. Lead encephalopathy: CT and MR findings. J Comput Assist Tomogr. 2002; 26, 479481.
5.Staudinger KC, Roth VS. Occupational lead poisoning. Am Fam Physician (Review) 1998; 57, 719726.
6.Bellinger DC, Stiles KM, Needleman HL. Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics. 1992; 90, 855861.
7.Canfield RL, Gendle MH, Cory-Slechta DA. Impaired neuropsychological functioning in lead-exposed children. Dev Neuropsychol. 2004; 26, 513540.
8.Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med. 2003; 348, 15171526.
9.Dietrich KN, Berger OG, Succop PA, Hammond PB, Bornschein RL. The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the cincinnati lead study Cohort following school entry. Neurotoxicol Teratol. 1993; 15, 3744.
10.Needleman HL, Gatsonis CA. Low-level lead exposure and the IQ of children. A meta-analysis of modern studies. JAMA. 1990; 263, 673678.
11.Wright JP, Dietrich KN, Ris MD, et al. Association of prenatal and childhood blood lead concentrations with criminal arrests in early adulthood. PLoS Med. 2008; 5, e101.
12.Ashburner J, Friston KJ. Voxel-based morphometry – the methods. Neuroimage. 2000; 11, 805821.
13.Le Bihan D, Mangin JF, Poupon C, et al. Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging. 2001; 13, 534546.
14.Beaulieu C. The basis of anisotropic water diffusion in the nervous system – a technical review. NMR Biomed. 2002; 15, 435455.
15.Kim JH, Budde MD, Liang HF, et al. Detecting axon damage in spinal cord from a mouse model of multiple sclerosis. Neurobiol Dis. 2006; 21, 626632.
16.Kinoshita Y, Ohnishi A, Kohshi K, Yokota A. Apparent diffusion coefficient on rat brain and nerves intoxicated with methylmercury. Environ Res. 1999; 80, 348354.
17.Song S-K, Sun S-W, Ju W-K, et al. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage. 2003; 20, 17141722.
18.Partridge SC, Mukherjee P, Henry RG, et al. Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns. Neuroimage. 2004; 22, 13021314.
19.Song S-K, Sun S-W, Ramsbottom MJ, et al. Dysmyelination revealed through MRI as increased radial (but Unchanged Axial) diffusion of water. Neuroimage. 2002; 17, 14291436.
20.Song S-K, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005; 26, 132140.
21.Suzuki Y, Matsuzawa H, Kwee IL, Nakada T. Absolute eigenvalue diffusion tensor analysis for human brain maturation. NMR Biomed. 2003; 16, 257260.
22.Dietrich KN, Succop PA, Berger OG, Hammond PB, Bornschein RL. Lead exposure and the cognitive development of urban preschool children: the cincinnati lead study cohort at age 4 years. Neurotoxicol Teratol. 1991; 13, 203211.
23.Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med. 2008; 5, e112.
24.Brubaker CJ, Dietrich KN, Lanphear BP, Cecil KM. The influence of age of lead exposure on adult gray matter volume. Neurotoxicology. 2010; 31, 259266.
25.Cecil KM, Dietrich KN, Altaye M , et al. Proton magnetic resonance spectroscopy in adults with childhood lead exposure. EHP (in press).
26.Brubaker CJ, Schmithorst VJ, Haynes EN, et al. Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study. Neurotoxicology. 2009; 30, 867875.
27.Yuan W, Holland SK, Cecil KM, et al. The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function. Pediatrics. 2006; 118, 971977.
28.Toscano CD, Guilarte TR. Lead neurotoxicity: from exposure to molecular effects. Brain Res Rev. 2005; 49, 529554.
29.Guilarte TR, Miceli RC, Jett DA. Neurochemical aspects of hippocampal and cortical Pb2+ neurotoxicity. Neurotoxicology. 1994; 15, 459466.
30.Deng W, Poretz RD. Lead exposure affects levels of galactolipid metabolic enzymes in the developing rat brain. Toxicol Appl Pharmacol. 2001; 172, 98107.
31.Zawia NH, Harry GJ. Exposure to lead-acetate modulates the developmental expression of myelin genes in the rat frontal lobe. Int J Dev Neurosci. 1995; 13, 639644.
32.Toews AD, Blaker WD, Thomas DJ, et al. Myelin deficits produced by early postnatal exposure to inorganic lead or triethyltin are persistent. J Neurochem. 1983; 41, 816822.
33.Toews AD, Krigman MR, Thomas DJ, Morell P. Effect of inorganic lead exposure on myelination in the rat. Neurochem Res. 1980; 5, 605616.
34.Deng W, Poretz RD. Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells. Brain Res. 2002; 929, 8795.
35.Dabrowska-Bouta B, Struzynska L, Walski M, Rafalowska U. Myelin glycoproteins targeted by lead in the rodent model of prolonged exposure. Food Chem Toxicol. 2008; 46, 961966.
36.Dabrowska-Bouta B, Sulkowski G, Bartosz G, Walski M, Rafalowska U. Chronic lead intoxication affects the myelin membrane status in the central nervous system of adult rats. J Mol Neurosci. 1999; 13, 127139.
37.Selvin-Testa A, Loidl CF, Lopez-Costa JJ, Lopez EM, Pecci-Saavedra J. Chronic lead exposure induces astrogliosis in hippocampus and cerebellum. Neurotoxicology. 1994; 15, 389401.
38.Struzynska L, Bubko I, Walski M, Rafalowska U. Astroglial reaction during the early phase of acute lead toxicity in the adult rat brain. Toxicology. 2001; 165, 121131.
39.Struzynska L, Dabrowska-Bouta B, Koza K, Sulkowski G. Inflammation-like glial response in lead-exposed immature rat brain. Toxicol Sci. 2007; 95, 156162.
Recommend this journal

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

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 3
Total number of PDF views: 10 *
Loading metrics...

Abstract views

Total abstract views: 91 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd October 2017. This data will be updated every 24 hours.