Abstract
Lead is arguably the most studied of the neurotoxicants (Silbergeld, 1992; Dietrich, 1995). Epidemiological and experimental studies of the toxic effects and mechanisms of action of lead have grown exponentially since the 1960s and 1970s. This work has produced an unparalleled body of scientific information on the effects of lead on the central nervous system (CNS). This chapter provides a brief review of the current knowledge and the key hypotheses about the toxicity of lead to the central nervous system (CNS).
An enormous amount of lead has been released to the environment through human activities since the 1920s, when tetraethyl lead was first sold as an antiknock agent in gasoline for automobile engines. The use of inorganic lead as an anticorrosive agent in paints and primers represents another important source of lead released to the environment. These practices are largely responsible for widespread and persistent environmental contamination often exceeding concentrations now known to have the potential to cause serious harm to human health.
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AAP. (2005) Lead exposure in children: Prevention, detection, and management. American Academy of Pediatrics, Committee on environmental health. Pediatrics 116(4): 1036-1046
Adams, R.D. and M. Victor. (1993) Principles of neurology. 5th ed., McGraw-Hill, NewYork
Agre, P., L.S. King, M. Yasui, W.B. Guggino, O.P. Ottersen, Y. Fujiyoshi, A. Engel and S. Nielsen. (2002) Aquaporin water channels: From atomic structure to clinical medicine. J. Physiol. 542: 3–16
al Khayat, A., N.S. Menon and M.R. Alidina. (1997) Acute lead encephalopathy in early infancy: clinical presentation and outcome. Ann. Trop. Paediatr. 17: 39–44
Atre, A.L., P.R. Shinde, S.N. Shinde, R.S. Wadia, A.A. Nanivadekar, S.J. Vaid and R.S. Shinde. (2006) Pre- and post-treatment MR imaging findings in lead encephalopathy. AJNR Am. J. Neuroradiol. 27: 902–903
Audesirk, G. and T. Audesirk. (1993) The effects of inorganic lead on voltage sensitive calcium channels differ among cell types and among channel subtypes. Neurotoxicology 14: 259–265
Badaut, J., F. Lasbennes, P.J. Magistretti and L. Regli. (2002) Aquaporins in brain: Distribution, physiology, and pathophysiology. J. Cereb. Blood Flow Metab. 22: 367–378
Baghurst, P.A., A.J. McMichael, N.R. Wigg, G.V. Vimpani, E.F. Robertson, R.J. Roberts and S.L. Tong. (1992) Environmental exposure to lead and children’s intelligence at the age of seven years: The Port Pirie cohort study. N. Engl. J. Med. 327: 1279–1284
Barone, S.Jr, M.E. Stanton and W.R. Mundy. (1995) Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging. Neurobiol. Aging 16: 723–735
Basha, M.R., W. Wei, G.R. Reddy, and N.H. Zawia. (2004) Zinc finger transcription factors mediate perturbations of brain gene expression elicited by heavy metals. In: Molecular Neurotoxicology, Environmental Agents, and Transcription-Transduction Coupling. N.H. Zawia (editor), CRC Press, Boca Raton, pp 43–64
Basha, M.R., W. Wei, S.A. Bakheet, N. Benitez, H.K. Siddiqi, Y.W. Ge, D.K. Lahiri and N.H. Zawia. (2005) The fetal basis of amyloidogenesis: Exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J. Neurosci. 25: 823–829
Bates, D.O. and F.E. Curry. (1996) Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels. Am. J. Physiol. 271: H2520–H2528
Bates, D.O. and F.E. Curry. (1997) Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway. Am. J. Physiol. 273: H687–H694
Bellinger, D.C. (2004) Lead. Pediatrics 113: 1016–1022
Bellinger, D.C. and H.L. Needleman. (2003) Intellectual impairment and blood lead levels. N. Engl. J. Med. 349: 500–502
Bellinger, D.C., K.M. Stiles and H.L. Needleman. (1992) Low-level lead exposure, intelligence and academic achievement: A long-term follow-up study. Pediatrics 90: 855–861
Bernal, J., J.H. Lee, L.L. Cribbs and E. Perez-Reyes. (1997) Full reversal of Pb<Superscript>2+</Superscript> block of L-type Ca<Superscript>2+</Superscript> channels requires treatment with heavy metal antidotes. J. Pharmacol. Exp. Ther. 282: 172–180
Bolin, C.M., R. Basha, D. Cox, N.H. Zawia, B. Maloney, D.K. Lahiri, and F. Cardozo-Pelaez. (2006) Exposure to lead (Pb) and the developmental origin of oxidative DNA damage in the aging brain. FASEB J. 20(6): 788–790
Bouton, C.M., L.P. Frelin, C.E. Forde, H.A. Godwin and J. Pevsner. (2001a) Synaptotagmin I is a molecular target for lead. J. Neurochem. 76: 1724–1735
Bouton, C.M., M.A. Hossain, L.P. Frelin, J. Laterra, and J. Pevsner. (2001b) Microarray analysis of differential gene expression in lead-exposed astrocytes. Toxicol. Appl. Pharmacol. 176: 34–53
Bradbury, M.W. and R. Deane. (1993) Permeability of the blood-brain barrier to lead. Neurotoxicology 14: 131–136
Bressler, J.P. and G.W. Goldstein. (1991) Mechanisms of lead neurotoxicity. Biochem. Pharmacol. 41: 479–484
Bressler, J., K. Kim, T. Chakraborti and G. Goldstein. (1999) Molecular mechanisms of lead neurotoxicity. Neurochem. Res. 24(4): 595–600
Burdo, J.R., J. Martin, S.L. Menzies, K.G. Dolan, M.A. Romano, R.J. Fletcher, M.D. Garrick, L.M. Garrick and J.R. Connor. (1999) Cellular distribution of iron in the brain of the Belgrade rat. Neuroscience 93: 1189–1196
Burns, C.B. and B. Currie. (1995) The efficacy of chelation therapy and factors influencing mortality in lead intoxicated petrol sniffers. Aust. N. Z. J. Med. 25: 197–203
Bush, A.I. (2003) The metallobiology of Alzheimer’s disease. Trends Neurosci. 26: 207–214
Cairney, S., P. Maruff, C. Burns and B. Currie. (2002) The neurobehavioural consequences of petrol (gasoline) sniffing. Neurosci. Biobehav. Rev. 26: 81–89
Cairney, S., P. Maruff, C.B. Burns, J. Currie and B.J. Currie. (2004a) Saccade dysfunction associated with chronic petrol sniffing and lead encephalopathy. J Neurol Neurosurg. Psychiatr. 75: 472–476
Cairney, S., P. Maruff, C.B. Burns, J. Currie and B.J. Currie. (2004b) Neurological and cognitive impairment associated with leaded gasoline encephalopathy. Drug Alcohol Depend. 73: 183–188
Cairney, S., P. Maruff, C.B. Burns, J. Currie and B.J. Currie. (2005) Neurological and cognitive recovery following abstinence from petrol sniffing. Neuropsychopharmacol. 30: 1019–1027
Canfield, R.L., C.R. Henderson, D.A. Cory-Slechta, C. Cox, J.A. Jusko and B.P. Lanphear. (2003) Intellectual impairment in children with blood lead concentrations below 10 micrograms per deciliter. N. Engl. J. Med. 348: 1517–1526
CDC. (1991) Preventing lead poisoning in young children: A statement by the Centers for Disease Control. Centers for Disease Control and Prevention, Atlanta, GA
CDC. (2002) Managing elevated blood lead levels among young children: Recommendations from the Advisory Committee on Childhood Lead Poisoning Prevention. Centers for Disease Control and Prevention, Atlanta, GA. www.cdc.gov/nceh/lead/CaseManagement/caseManage_main.htm.
Chen, A., K.N. Dietrich, J.H. Ware, J. Radcliffe and W.J. Rogan. (2005) IQ and blood lead from 2 to 7 years of age: are the effects in older children the residual of high blood lead concentrations in 2-year-olds? Environ. Health Perspect. 113(5): 597–601
Chisolm, J.J.Jr. and H.E. Harrison. (1956) The exposure of children to lead. Pediatrics 18: 943–957
Chisolm, J.J.Jr and E. Kaplan. (1968) Lead poisoning in childhood comprehensive management and prevention. J. Pediatr. 73: 942–950
Christian, J.R., B.S. Celewycz and S.H. Andelman. (1964) A three-year study of lead poisoning in Chicago. Am. J. Public Health 54: 1241–1245
Clark, C.S., R.L. Bornschein, P. Succop, S.S. Que Hee, P.B. Hammond and B. Peace. (1985) Condition and type of housing as an indicator of potential environmental lead exposure and pediatric blood lead levels. Environ. Res. 38: 46–53
Cory-Slechta, D.A. (1997) Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity. Neurotoxicology 18: 673–688
Cory-Slechta, D.A. and H.H. Schaumburg. (2000) Lead, inorganic. In: Experimental and Clinical Neurotoxicology (second edition), P.S. Spencer, H.H. Schaumburg, A.C. Ludolph (editors). Oxford University Press, New York, pp. 708–720
Crair, M.C. and R.C. Malenka. (1995) A critical period for long-term potentiation at thalamocortical synapses. Nature 375: 325–328
Currie, B., J. Burrow, D. Fisher, D. Howard, M. McEiver and C. Burns. (1994) Petrol sniffer’s encephalopathy. Med. J. Aust. 160: 800
Dietrich, K.N. (1995) A higher level of analysis: Bellinger’s, interpreting the literature on lead and child development. Neurotoxicol. Teratol. 17: 223–225
Dietrich, K.N. (1999) Environmental neurotoxicants and psychological development. In: Pediatric Neuropsychology: Research, Theory and Practice. G. Taylor, D. Ris and K.O. Yeates (editors). Guilford Press, New York, pp. 206–34
Dietrich, K.N., O.G. Berger, P.A. Succop, P.B. Hammond and R.L. Bornschein. (1993) 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. 15: 37–44
Dietrich, K.N., O.G. Berger, A. Bhattacharya. (2000) Symptomatic lead poisoning in infancy: A prospective case analysis. J. Pediatr. 137: 568–571
Dietrich, K.N., M.D. Ris, P.A. Succop, O.G. Berger and R.L. Bornschein. (2001) Early exposure to lead and juvenile delinquency. Neurotoxicol. Teratol. 23: 511–518
Dietrich, K.N., J.H. Ware, M. Salganik, J. Radcliffe, W.J. Rogan, G.G. Rhoads, M.E. Fay, C.T. Davoli, M.B. Denckla, R.L. Bornschein, D. Schwarz, D.W. Dockery, S. Adubato and R.L. Jones. (2004) Effect of chelation therapy on the neuropsychological and behavioral development of lead exposed children after school entry. Pediatrics 114: 19–26
Ernhart, C.B., M. Morrow-Tlucak, A.W. Wolf, D. Super and D. Drotar. (1989) Low level lead exposure in the prenatal and early preschool periods: Intelligence prior to school entry. Neurotoxicol. Teratol. 11: 161–170
Factor-Litvak, P., G. Wasserman, J.K. Kline and J. Graziano. (1999) The Yugoslavia prospective study of environmental lead exposure. Environ. Health Perspect. 107: 9–15
Feldman, R.G. and R.F. White. (1992) Lead neurotoxicity and disorders of learning. J. Child Neurol. 7: 354–359
Fergusson, D.L., Horwood and M. Lynskey. (1997) Early dentine lead levels and educational outcomes at 18 years. J. Child Psychol. Psychiatr. 38: 471–478
Finkelstein, Y., M.E. Markowitz and J.F. Rosen. (1998) Low-level lead-induced neurotoxicity in children: An update on central nervous system effects. Brain Res. Rev. 27: 168–176
Fischbein, A. (1998) Occupational and environmental exposure to lead. In: Environmental and Occupational Medicine. W. Rom (editor), Lippincott-Raven, Philadelphia, pp. 973–996
Fulton, M., G. Raab, G. Thomson, D. Laxen, R. Hunter, W. Hepburn. (1987) Influence of blood lead on the ability and attainment of children in Edinburgh. Lancet 1: 1221–1226
Gabbita, S.P., M.A. Lovell and W.R. Markesbery. (1998) Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J. Neurochem. 71: 2034–2040
Goldstein, G.W. (1990) Lead poisoning and brain cell function. Environ. Health Perspect. 89: 91–94
Goldstein, G.W. and D. Ar. (1983) Lead activates calmodulin sensitive processes. Life Sci. 33: 1001–1006
Goldstein, G.W., A.K. Asbury and I. Diamond. (1974) Pathogenesis of lead encephalopathy: Uptake of lead and reaction of brain capillaries. Arch. Neurol. 31: 382–389
Goodheart, R.S. and J.W. Dunne. (1994) Petrol sniffer’s encephalopathy. Med. J. Aust. 160: 178–181
Gordon, R.A., G. Roberts, Z. Amin, R.H. Williams and F.P. Paloucek. (1998) Aggressive approach in the treatment of acute lead encephalopathy with an extraordinarily high concentration of lead. Arch. Pediatr. Adolesc. Med. 152: 1100–1104
Gunnarson, E., G. Axehult, G. Baturina, S. Zelenin, M. Zelenina and A. Aperia. (2005) Lead induces increased water permeability in astrocytes expressing Aquaporin 4. Neuroscience 136: 105–114
Gunshin, H., B. Mackenzie, U.V. Berger, Y. Gunshin, M.F. Romero, W.F. Boron, S. Nussberger, J.L. Gollan and M.A. Hediger. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388: 482–488
Habermann, E., K. Crowell, P. Janicki. (1983) Lead and other metals can substitute for Ca<Superscript>2+</Superscript> in calmodulin. Arch. Toxicol. 54: 61–70
Hackley, B. and A. Katz-Jacobson. (2003) Lead poisoning in pregnancy: A case study with implications for midwives. Journal of Midwifery and Women’s Health 48(1): 30–38
Holstege, C.P., J.D. Ferguson, C.E. Wolf, A.B. Baer and A. Poklis. (2004) Analysis of moonshine for contaminants. J. Toxicol. 42(5): 597–601
Holtzman, D., C. DeVries, H. Nguyen, J.H. Jameson, J. Olson, M. Carrithers and K. Bensch. (1982) Development of resistance to lead encephalopathy during maturation in the rat pup. J. Neuro. Exp. Neuro. 41: 652–663
Holtzman, D., C. DeVries, H. Nguyen, J. Olson and K. Bensch. (1984) Maturation of resistance to encephalopathy: Cellular and subcellular mechanism. Neurotoxicology 5: 97–124
Hossain, M.A., J.C. Russell, S. Miknyoczki, B. Ruggeri, B. Lal and J. Laterra. (2004) Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy. Ann. Neurol. 55(5): 660–667
Huang, E., W.Y. Ong and J.R. Connor. (2004) Distribution of divalent metal transporter-1 in the monkey basal ganglia. Neuroscience 128: 487–496
Huang, E. and W.Y. Ong. (2005) Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury. Exp. Brain Res. 161: 502–511
Ide-Ektessabi, A., Y. Ota, R. Ishihara, Y. Mizuno and T. Takeuchi. (2005) Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams. Nucl. Instrum. Methods Phys. Res. B 241: 681–684
Johnston, M.V. (2003) Brain plasticity in paediatric neurology. Eur. J. Paediatr. Neurol. 7: 105–113
Johnston, M.V. (2004) Clinical disorders of brain plasticity. Brain and Develop. 26: 73–80
Johnston, M.V. and G.W. Goldstein. (1998) Selective vulnerability of the developing brain to lead. Curr. Opin. Neurol. 11: 689–693
Johnston, M.V., A. Nishimura, K. Harum, J. Pekar and M.E. Blue. (2001) Sculpting the developing brain. Adv. Pediatr. 48: 1–38
Johnston, M.V., L. Alemi and K.H. Harum. (2003) Learning, memory and transcription factors. Pediatr. Res. 53: 369–74
Jung, J.S., R.V. Bhat, G.M. Preston, W.B. Guggino, J.M. Baraban and P. Agre. (1994) Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc. Natl. Acad. Sci. USA 91: 13052–13056
Kaelan, C., C. Harper and B. Vieira. (1986) Acute encephalopathy and death due to petrol sniffing: Neuropathological findings. Aust. N. Z. J. Med. 16: 804–807
Kerper, L.E. and P.M. Hinkle. (1997a) Lead uptake in brain capillary endothelial cells: activation by calcium store depletion. Toxicol. Appl. Pharmacol. 146: 127–133
Kerper, L.E. and P.M. Hinkle. (1997b) Cellular uptake of lead is activated by depletion of intracellular calcium stores. J. Biol. Chem. 272: 8346–8352
Kim, K.A., T. Chakraborti, G.W. Goldstein and J.P. Bressler. (2000) Immediate early gene expression in PC-12 cells exposed to lead: Requirement for protein kinase C. J. Neurochem. 74: 1140–1146
Kim, S.A., T. Chakraborti, G. Goldstein, M. Johnston and J. Bressler. (2002) Exposure of lead elevates induction of Zif268 and Arc mRNA in rats after electroconvulsive shock: The involvement of PKC. J. Neurosci. Res. 69: 268–277
Kimelberg, H.K. (1995) Current concepts of brain edema: Review of laboratory investigations. J. Neurosurg. 83: 1051–1059
Kovalchuk, Y., E. Hanse, K.W. Kafitz and A. Konnerth. (2002) Postsynaptic induction of BDNF-mediated long-term potentiation. Science 295: 1729–1734
Landrigan, P.J. and A.C. Todd. (1995) Lead poisoning. West. J. Med. 161: 153–159
Lanphear, B.P., K. Dietrich, P. Auinger and C. Cox. (2000) Cognitive deficits associated with blood lead levels < 10 μg/dl in US children and adolescents. Public Health Rep. 115: 521–529
Lanphear, B.P., R. Hornung, M. Ho, C.R. Howard, S. Eberly and K. Knauf. (2002) Environmental lead exposure during early childhood. J. Pediatr. 140: 40–47
Lasley, S.M. and M.E. Gilbert. (2002) Rat hippocampal glutamate and GABA release exhibit biphasic effects as a function of chronic lead exposure level. Toxicol. Sci. 66: 139–47
Laterra, J., J.P. Bressler, R.R. Indurti, L. Belloni-Olivi and G.W. Goldstein. (1992) Inhibition of astroglial-induced endothelial differentiation by inorganic lead: A role for protein kinase C. Proc. Natl. Acad. Sci. USA 89: 10748–10752
Lee, W.T., H. Yoon, D.J. Lee, C.H. Koo and K.A. Park. (2002) Effects of postnatally administered inorganic lead on the tyrosine hydroxylase immunoreactive norepinephrinergic neurons of the locus ceruleus of the rat. Arch. Histol. Cytol. 65: 45–53
Leggett, R.W. (1993) An age-specific kinetic model of lead metabolism in humans. Environ. Health Perspect. 101: 598–616
Leung, D.W., G. Cachianes, W.J. Kuang, and N. Ferrara. (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246: 1306–1309
Lidsky, T.I. and J.S. Schneider. (2003) Lead neurotoxicity in children: Basic mechanisms and clinical correlates. Brain. 126: 5–19
Lindahl, L.S., L. Bird, M.E. Legare, G. Mikeska, G.R. Bratton and E. Tiffany-Castiglioni. (1999) Differential ability of astroglia and neuronal cells to accumulate lead: Dependence on cell type and on degree of differentiation. Toxicol. Sci. 50: 236–243
Links, J.M., B.S. Schwartz, D. Simon, K. Bandeen-Roche and W.F. Stewart. (2001) The influence of toxicant “residence time” and bioavailability from body stores in estimation of cumulative target organ dose: Application to lead-associated neurocognitive decline. Environ. Health Perspect. 109: 361–368
Liu, X., K.N. Dietrich, J. Radcliffe, N.B. Ragan, G.G. Rhoads and W.J. Rogan. (2002) Do children with falling blood lead levels have improved cognition. Pediatrics 110: 787–791
Lovell, M.A., S.P. Gabbita and W.R. Markesbery. (1999) Increased DNA oxidation and decreased levels of repair products in Alzheimer’s disease ventricular CSF. J. Neurochem. 72: 771–776
Lu, T., Y. Pan, S.Y. Kao, C. Li, I. Kohane, J. Chan and B. Yankner. (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429: 883–891
Malinow, R. and R.C. Malenka. (2002) AMPA receptor trafficking and synaptic plasticity. Annu. Rev. Neurosci. 25: 103–26
Mani, J., N. Chaudhary, M. Kanjalkar and P.U. Shah. (1998) Cerebellar ataxia due to lead encephalopathy in an adult. J. Neurol. Neurosurg. Psychiatr. 65: 797–798
Markovac, J. and G.W. Goldstein. (1988a) Lead activates protein kinase C in immature rat brain microvessels. Toxicol. Appl. Pharmacol. 96: 14–23
Markovac, J. and G.W. Goldstein. (1988b) Picomolar concentrations of lead stimulate brain protein kinase C. Nature 334: 71–73
Markowitz, M. (2000) Lead Poisoning. Pediatr. Rev. 21: 327–35
McCall, R.B. (1983) A conceptual approach to early mental development. In: Origins of Intelligence. M. Lewis (editor). Plenum Press, New York, pp. 107–133
McDonald, J.W. and M.V. Johnston. (1990) Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res. Rev. 15: 41–70
Mendola, P., S.G. Selevan, S. Gutter and D. Rice. (2002) Environmental factors associated with a spectrum of neurodevelopmental deficits. Ment. Retard. Dev. Disabil. 8: 188–197
Minnema, D.J., R.D. Greenland and I.A. Michaelson. (1986) Effect of in vitro inorganic lead on dopamine release from superfused rat striatal synaptosomes. Toxicol. Appl. Pharmacol. 84: 400–411
Needleman, H.L. and C.A. Gatsonis. (1990) Low-level lead exposure and the IQ of children: A meta-analysis of modern studies. JAMA 263: 673–678
Needleman, H.L., C. Gunnoe, A. Leviton, R. Reed, H. Peresie, C. Maher and P. Barrett. (1979) Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N. Engl. J. Med. 300: 689–695
Needleman, H.L., A. Schell, D. Bellinger, A. Leviton and E.N. Allred. (1990) The long-term effects of exposure to low doses of lead in childhood: An 11-year follow-up report. N. Engl. J. Med. 322: 83–88
Needleman, H.L. J.A. Riess, M.J. Tobin, G.E. Biesecker and J.B. Greenhouse. (1996) Bone lead levels and delinquent behavior. JAMA 275: 363–369
Needleman, H.L., C. McFarland, R.B. Ness, S.E. Fienberg and M.J. Tobin. (2002) Bone lead levels in adjudicated delinquents. A case control study. Neurotoxicol. Teratol. 24: 711–717
Nicchia, G.P., A. Frigeri, G.M. Liuzzi, M.P. Santacroce, B. Nico, G. Procino, F. Quondamatteo, R. Herken, L. Roncali and M. Svelto. (2000) Aquaporin-4-containing astrocytes sustain a temperature- and mercury-insensitive swelling in vitro. Glia 31: 29–38
Nielsen, S., E.A. Nagelhus, M. Amiry-Moghaddam, C. Bourque, P. Agre and O.P. Ottersen. (1997) Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J. Neurosci. 17: 171–180
Niemietz, C.M. and S.D. Tyerman. (2002) New potent inhibitors of aquaporins: Silver and gold compounds inhibit aquaporins of plant and human origin. FEBS Lett. 531: 443–447
Ong, W.Y. and A.A. Farooqui. (2005) Iron, neuroinflammation, and Alzheimer’s disease. J. Alzheimer’s Dis. 8: 183–200
Ong, W.Y., M.Q. Ren, J. Makjanic, T.M. Lim and F. Watt. (1999) A nuclear microscopic study of elemental changes in the rat hippocampus after kainate-induced neuronal injury. J. Neurochem. 72: 1574–1579
Ong, W.Y., X. He, L.H. Chua and C.N. Ong. (2006) Increased uptake of divalent metals lead and cadmium into the brain after kainite-induced neuronal injury. Exp. Brain Res. 173: 468–474
Papanikolaou, N.C., E.G. Hatzidaki, S. Belivanis, G.N. Tzanakakis, A.M. Tsatsakis. (2005) Lead toxicity update: A brief review. Med. Sci. Monit. 11(10): RA329–RA336
Peng, S., R.K. Hajela and W.D. Atchison. (2002) Characteristics of block by Pb<Superscript>2+</Superscript> of function of human neuronal L-, N-, and R-type Ca<Superscript>2+</Superscript> channels transiently expressed in human embryonic kidney cells. Mol. Pharmacol. 62: 1418–1430
Penn, A.A. and C.J. Shatz. (1999) Brain waves and brain wiring: The role of endogenous and sensory driven neural activity in development. Pediatr. Res. 45: 447–458
Pentschew, A. and F. Garro. (1966) Lead encephalomyelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases: With special reference to the permeability disorders of the nervous system capillaries. Acta Neuropathol. 6: 266–278
Perelman, S., L. Hertz-Pannier, M. Hassan, and A. Bourrillon. (1993) Lead encephalopathy mimicking a cerebellar tumor. Acta Paediatr. 82: 423–425
Perlstein, M.A. and R. Attala. (1966) Neurologic sequelae of plumbism in children. Clin. Pediatr. 5: 292–298
Philip, A.T. and B. Gerson. (1994) Lead poisoning — Part I. Clin. Lab. Med. 14: 423–44
Pocock, S.J., M. Smith and P. Baghurst. (1994) Environmental lead and children’s intelligence: A systematic review of the epidemiological evidence. Br. Med. J. 309: 1189–1197
Press, M.F. (1977) Lead encephalopathy in neonatal long-evans rats: Morphologic studies. J. Neuropathol. Exp. Neurol. 36: 169–193
Preston, G.M., T.P. Carroll, W.P. Guggino and P. Agre. (1992) Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 256: 385–387
Raff, M.C., B.A. Barres, J.F. Burne, H.S. Coles, Y. Ishizaki, and M.D. Jacobson. (1993) Programmed cell death and the control of cell survival: Lessons from the nervous system. Science 262: 695–700
Regan, C.M. (1989) Lead-impaired neurodevelopment: Mechanisms and threshold values in the rodent. Neurotoxicol. Teratol. 11: 533–537
Regan, C.M. (1991) Neural cell adhesion molecules: Neuronal development, and lead toxicity. In: Proceedings, Ninth International Neurotoxicology Conference, J. Cranmer (editor), Little Rock
Regan, C.M. (1993) Neural cell adhesion molecules, neuronal development and lead toxicity. Neurotoxicology 14: 69–76
Reyes, P.F., C.F. Gonzalez, M.K. Zalewska and A. Besarab. (1986) Intracranial calcification in adults with chronic lead exposure. AJR Am. J. Roentgenol. 146: 267–270
Rice, D. (1989) Delayed neurotoxicity in monkeys exposed developmentally to methyl mercury. Neurotoxicology. 10: 645–650
Rice, D.C. (1993) Lead-induced changes in learning: Evidence for behavioral mechanisms from experimental animal studies. Neurotoxicology 14: 167–178
Rogan, W.J., K.N. Dietrich, J.H. Ware, D.W. Dockery, M. Salganik, J. Radcliffe, R.L. Jones, N.B. Ragan, J.J. Chisolm and G.G. Rhoads. (2001) The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. N. Engl. J. Med. 344: 1421–1426
Roger, S.D., D. Crimmins, C. Yiannikas and D.C. Harris. (1990) Lead intoxication in an anuric patient: Management by intraperitoneal EDTA. Aust. N. Z. J. Med. 20: 814–817
Rowland, A.S. and R.C. McKinstry. (2006) Lead toxicity, white matter lesions, and aging. Neurology 66: 1464–1465
Ruff, H.A., P.E. Bijur, M. Markowitz, Y.C. Ma and J.F. Rosen. (1993) Declining blood lead levels and cognitive changes in moderately lead-poisoned children. JAMA 269: 1641–1646
Ruff, H.A., M.E. Markowitz, P.E. Bijur and J. Rosen. (1996) Relationships among blood lead levels, iron deficiency and cognitive development in two-year-old children. Environ. Health Perspect. 104(2): 180–185
Sanchez-Ramos, J., E. Overvik and B. Ames. (1994) A marker of oxyradical-mediated DNA damage (8-hydroxy-2′-deoxyguanosine) is increased in nigrostriatum of Parkinson′s disease brain. Neurodegen. 3: 197–204
Saper, R.B., S.N. Kales, J. Paquin, M.J. Burns, D.M. Eisenberg, R.B. Davis and R.S. Phillips. (2004) Heavy metal content of ayurvedic herbal medicine products. JAMA 292: 2868–2873
Saryan, L.A. and C. Zenz. (1994) Lead and its compounds. In: Occupational Medicine (third edition). L.A. Saryan and C. Zenz (editors), Mosby, St. Louis, pp. 506–541
Schwartz, J. (1994) Low-level lead exposure and children’s IQ: A meta-analysis and search for a threshold. Environ. Res. 65: 42–55
Schwartz, B.S., W.F. Stewart, K.I. Bolla, D. Simon, K. Bandeen-Roche, B. Gordon, J.M. Links, A.C. Todd, W. Shi, S. Bassett and P. Youssem. (2000) Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology. 55: 1144–1150
Sciarillo, W.G., G. Alexander and K.P. Farrell. (1992) Lead exposure and child behavior. Am. J. Public Health. 82: 1356–1360
Sheng, M. and M.J. Kim. (2002) Postsynaptic signaling and plasticity mechanisms. Science. 298: 776–80
Silbergeld, E.K. (1992) Mechanisms of lead neurotoxicity, or looking beyond the lamppost. FASEB J. 6: 3201–3206
Stewart, W.F., B.S. Schwartz, D. Simon, K.I. Bolla, A.C. Todd and J. Links. (1999) The relation between neurobehavioral function and tibial and chelatable lead levels in former organolead manufacturing workers. Neurology. 52: 1610–1617
Stewart, W.F., B.S. Schwartz, C. Davatzikos, D. Shen, D. Liu, X. Wu, A.C. Todd, W. Shi, S. Bassett and D. Youssem. (2006) Past adult lead exposure is linked to neurodegeneration measured by brain MRI. Neurology. 66: 1476–1484
Sweatt, J.D. (2001) The neuronal MAP kinase cascade: A biochemical signal integration system subserving synaptic plasticity and memory. J. Neurochem. 76: 1–10
Teo, J.G.C., K.Y.C. Goh, A. Ahuja, H.K. Ng and W.S. Poon. (1997) Intracranial vascular calcifications, glioblastoma multiforme, and lead poisoning. AJNR Am. J. Neuroradiol. 18: 576–579
Tiffany-Castiglioni, E., E.M. Sierra, J.-N. Wu and T.K. Rowles. (1989) Lead toxicity in neuroglia. Neurotoxicology 10: 417–443
Toews, A.D., A. Kolber, J. Hayward, M.R. Krigman and P. Morell. (1978) Experimental lead encephalopathy in the suckling rat: Concentration of lead in cellular fractions enriched in brain capillaries. Brain Res. 147: 131–138
Tong, S., P. Baghurst, A. McMichael, M. Sawyer and J. Mudge. (1996) Lifetime exposure to environmental lead and children’s intelligence at 11-13 years: The Port Pirie cohort study. Br. Med. J. 312: 1569–1575
Tong, S., P.A. Baghurst, M.G. Sawyer, J. Burns and A.J. McMichael. (1998) Declining blood lead levels and changes in cognitive function during childhood: The Port Pirie cohort study. JAMA 280: 1915–1919
Toscano, C.D., H. Hashemazadeh-Gargari, J.L. McGlothan and T.R. Guilarte. (2002) Developmental Pb(<Superscript>2+</Superscript>) exposure alters NMDA subtypes and reduces CREB phosphorylation in the rat brain. Dev. Brain Res. 139: 217–226
Tsai, Y.-T., C.-C. Huang, H.-C. Kuo, H.-M. Wang, W.-S. Shen, T.-S. Shih and N.-S. Chu. (2006) Central nervous system effects in acute thallium poisoning. Neurotoxicol. 27: 291–295
Valpey, R., M. Sumi, M. Copass and G. Goble. (1978) Acute and chronic progressive encephalopathy due to gasoline sniffing. Neurology 28: 507–510
Wang, W., M.J. Merrill and R.T. Borchardt. (1996) Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. Am. J. Physiol. 271: C1973–C1980
Wang, X.S., W.Y. Ong and J.R. Connor. (2001) A light and electron microscopic study of the iron transporter protein DMT-1 in the monkey cerebral neocortex and hippocampus. J. Neurocytol. 30: 353–360
Wang, X.S., W.Y. Ong and J.R. Connor. (2002a) A light and electron microscopic study of divalent metal transporter-1 distribution in the rat hippocampus, after kainate-induced neuronal injury. Exp. Neurol. 177: 193–201
Wang, X.S., W.Y. Ong and J.R. Connor. (2002b) Increase in ferric and ferrous iron in the rat hippocampus with time after kainate-induced excitotoxic injury. Exp. Brain Res. 143: 137–148
Wasserman, G.A., X. Liu, N.J. Lolacono, P. Factor-Litvak, J.K. Kline, D. Popovac, N. Morina, A. Musabegovic, N. Vrenezi, S. Capuni-Paracka, V. Lekic, E. Preteni-Redjepi, S. Hadzialjevic, V. Slavkovich and J.H. Graziano. (1997) Lead exposure and intelligence in 7-year-old children: The Yugoslavia prospective study. Environ. Health Perspect. 105: 956–962
Wasserman, G.A., X. Liu, D. Popovac, P. Factor-Litvak, J. Kline, C. Waternaux, N. Lolacono and J.H. Graziano. (2000) The Yugoslavia prospective lead study: Contributions of prenatal and postnatal lead exposure to early intelligence. Neurotoxicol. Teratol. 22: 811–818
Weiss, B. (1991) Cancer and the dynamics of neurodegenerative processes. Neurotoxicol. 12: 379–386
Wilson, M.A., M.V. Johnston, G.W. Goldstein and M.E. Blue. (2000) Neonatal lead exposure impairs development of rodent barrel field cortex. Proc. Natl. Acad. Sci. USA. 97: 5540–5545
WHO. (1995) Environmental health criteria 165, inorganic lead. World Health Organization International Programme for Chemical Safety, Geneva, Switzerland
Yasui, M., T.H. Kwon, M.A. Knepper, S. Nielsen and P. Agre. (1999) Aquaporin-6: An intracellular vesicle water channel protein in renal epithelia. Proc. Natl. Acad. Sci. USA 96: 5808–5813
Yule, W., R. Lansdown, I.B. Millar and M.A. Urbanowicz. (1981) The relationship between blood lead concentrations, intelligence and attainment in a school population: A pilot study. Dev. Med. Child Neurol. 23: 567–576
Zawia, N.H. (2003) Transcriptional involvement in neurotoxicity. Toxicol. Appl. Pharmacol. 190: 177–188
Zelenina, M., A.A. Bondar, S. Zelenin and A. Aperia. (2003) Nickel and extracellular acidification inhibit the water permeability of human Aquaporin-3 in lung epithelial cells. J. Biol. Chem. 278: 30037–30043
Zelenina, M., S. Tritto, A.A. Bondar, S. Zelenin and A. Aperia. (2004) Copper inhibits the water and glycerol permeability of Aquaporin-3. J. Biol. Chem. 279: 51939–51943
Ziegler, E.E., B.B. Edwards, R.I. Jensen, K.R. Mahaffey and S.J. Fomon. (1978) Absorption and retention of lead by infants. Pediatr. Res. 12: 29–34
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Boyer, I.J. (2009). Lead Encephalopathy. In: McCandless, D. (eds) Metabolic Encephalopathy. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79112-8_24
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