Elsevier

Neurologic Clinics

Volume 18, Issue 3, 1 August 2000, Pages 541-561
Neurologic Clinics

DEVELOPMENTAL CONSIDERATIONS OF NEUROTOXIC EXPOSURES

https://doi.org/10.1016/S0733-8619(05)70210-3Get rights and content

Section snippets

CONCEPTS REGARDING BRAIN DEVELOPMENT AND BEHAVIOR

The purpose of this article is to give the reader a perspective regarding developmental considerations in neurotoxicology. Many comprehensive papers have reviewed the extensive number of testing instruments available to assess neurobehavioral and cognitive development in neonates, infants, and children including measures emphasizing pediatric neurologic, developmental psychologic, and cognitive/information processing functions.3, 29, 56 The goal of this article is not to list or evaluate such

General Methodological Considerations

One goal central to developmental neurotoxicology is to establish a link between a potential neurotoxic exposure and specific adverse neurobehavioral outcomes in exposed children. To establish this link requires the synthesis of multiple sources of information. First, evidence regarding the potential neurotoxicity of the agent must be reviewed in both animal models and epidemiologic literature, with particular attention to the specific substance at a particular dose and duration within a

Mechanisms of Nicotine-Induced Brain Maldevelopment.

Nicotine is easily transferred across the placental membranes, and fetal cord serum concentrations have been found at levels at or above those in maternal serum.65 The developmental neurotoxicity of nicotine has been attributed to its action as a direct agonist at nicotinic cholinergic receptors, resulting in primary alterations in cholinergic neurotransmission and secondary changes in catecholamine, i.e., norepinephrine and dopamine and glutamate neurotransmission.93 Alterations in these

Lead

The definition of lead poisoning has fluctuated over time. Before 1970, it was generally assumed that blood lead levels in excess of 60 μg/dL were required to produce toxic effects in children.118 In 1986 the World Health Organization revised the acceptable limit to 20 μg/dL, and more recently, the Centers for Disease Control guidelines13 have revised the intervention level downward to 10 μg/dL. Approximately 17.2% of children in the United States ages 6 months to 5 years are believed to have

SYNTHESIS AND CONCLUSIONS

Evaluating the effects of neurotoxic agents on developing organisms can be complicated by many factors. It is important to consider the species being studied, the dose and route of neurotoxin exposure, the developmental stage of exposure, and the interactive effect of that neurotoxin with other environmental variables. Animal models afford the unique opportunity for focusing on the mechanisms of action and identifying particular brain structures and neurochemical systems affected by particular

First page preview

First page preview
Click to open first page preview

References (127)

  • C.D. Driscoll et al.

    Prenatal alcohol exposure: Comparability of effects in humans and animal models

    Neurotoxicol Teratol

    (1990)
  • C.L. Ehlers et al.

    Effects of neonatal exposure to nicotine on electrophysiological parameters in adult rats

    Pharmacol Biochem Behav

    (1997)
  • P. Eriksson et al.

    Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptions and in behaviour of adult mice

    Brain Res

    (2000)
  • P.A. Fried et al.

    A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marijuana, cigarettes, and alcohol

    Neurotoxicol Teratol

    (1992)
  • P.A. Fried et al.

    Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana

    Neurotoxicol Teratol

    (1999)
  • E. Friedman et al.

    Analysis of receptor-stimulated and basal guanine nucleotide binding to membrane G proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis

    Anal Biochem

    (1993)
  • P. Gressens et al.

    Cocaine-induced disturbances of corticogenesis in the developing murine brain

    Neurosci Lett

    (1992)
  • O.N. Hansen et al.

    A neuropsychological study of children with elevated dentine lead level: Assessment of the effect of lead in different socioeconomic groups

    Neurotoxicol Teratol

    (1989)
  • A. Igata

    Epidemiological and clinical features of Minamata disease

    Environ Res

    (1993)
  • K.L. Jones et al.

    Pattern of malformation in offspring of chronic alcoholic mothers

    Lancet

    (1973)
  • W.E. Kaye et al.

    Recall bias in disease status associated with perceived exposure to hazardous substances

    Ann Epidemiol

    (1994)
  • N.A. Krasnegor et al.

    Neurobehavioral test strategies for environmental exposures in pediatric populations

    Neurotoxicol Teratol

    (1994)
  • S.M. Lasley et al.

    Presynaptic glutamatergic function in dentate gyrus in vivo is diminished by chronic exposure to inorganic lead

    Brain Res

    (1996)
  • S.L. Leech et al.

    Prenatal substance exposure: Effect on attention and impulsivity of 6-year-olds

    Neurotoxic Teratol

    (1999)
  • J. Markovac et al.

    Lead activates protein kinase C in immature rat brain microvessels

    Toxicol Appl Pharmacol

    (1988)
  • J.S. Meyer et al.

    Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity

    Brain Res

    (1993)
  • K. Murata et al.

    Delayed evoked potentials in children exposed to methylmercury from seafood

    Neurotoxicol Teratol

    (1999)
  • M.G. Paule et al.

    Operant test battery performance in children: Correlation with IQ

    Neurotoxicol Teratol

    (1999)
  • J. Rossouw et al.

    Apparent central neurotransmitter receptor changes induced by low-level lead exposure during different developmental phases in the rat

    Toxicol Appl Pharmacol

    (1987)
  • Snyder-KellerA.M. et al.

    Prenatal cocaine increases striatal serotonin innervation without altering the patch/matrix organization of intrinsic cell types

    Dev Brain Res

    (1993)
  • L.P. Spear

    Neurobehavioral assessment during the early postnatal period

    Neurotoxicol Teratol

    (1990)
  • A. Stadlin et al.

    Postnatal changes in [3H]mazindol-labelled dopamine uptake sites in the rat striatum following prenatal cocaine exposure

    Brain Res

    (1994)
  • M.E. Stanton et al.

    Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity. Work Group I report: Comparability of measures of developmental neurotoxicity in humans and laboratory animals

    Neurotoxicol Teratol

    (1990)
  • AkbariH.M. et al.

    Increased tyrosine hydroxylase immunoreactivity in the rat cortex following prenatal cocaine exposure

    Dev Brain Res

    (1992)
  • M. Aschner

    Methylmercury in astrocytes: What possible significance

    Neurotoxicol

    (1996)
  • G. Axelsson et al.

    Use of questionnaires in occupational studies of pregnancy outcomes: Validation of questionnaire reported miscarriage, malformation, and birth weight

    Int J Epidemiol

    (1984)
  • I.S. Baron et al.

    Pediatric Neuropsychology in the Medical Setting

  • D. Bellinger et al.

    Longitudinal analysis of prenatal and postnatal lead exposure in early cognitive development

    N Engl J Med

    (1987)
  • D. Bellinger et al.

    Antecedents and correlates of improved cognitive performance in children exposed in utero to low levels of lead

    Environ Health Perspect

    (1990)
  • N.G. Beratis et al.

    Cord blood alpha-fetaprotein concentration in term newborns of smoking mothers

    Eur J Pediatr

    (1999)
  • N.R. Butler et al.

    Smoking in pregnancy and subsequent child development

    Br Med J

    (1973)
  • Centers for Disease Control

    Preventing Lead Poisoning in Young Children: A Statement by the Centers for Disease Control

  • E. Cernichiari et al.

    The biological monitoring of mercury in the Seychelles study

    Neurotoxicology

    (1995)
  • M.E. Charness

    Molecular mechanisms of ethanol intoxication, tolerance, and physical dependence

  • I.J. Chasnoff et al.

    Cocaine/poly-drug use in pregnancy: Two year follow-up

    Pediatrics

    (1992)
  • I.J. Chasnoff et al.

    Prenatal exposure to cocaine and other drugs: Outcome at four to six years

    Ann New York Acad Sci

    (1998)
  • C.A. Chiriboga et al.

    Neurological correlates of fetal cocaine exposure: Transient hypertonia of infancy and early childhood

    Pediatrics

    (1995)
  • C.A. Chiriboga

    Neurological correlates of fetal cocaine exposure

    Ann New York Academy of Sci

    (1998)
  • B.H. Choi et al.

    Abnormal neuronal migration, deranged cortical organization, and diffuse white matter astrocytosis of human fetal brain: A major effect of methylmercury poisoning in utero

    J Neuropathol Exp Neurol

    (1978)
  • D.A. Cory-Slecta

    Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity

    Neurotoxicology

    (1997)
  • Cited by (33)

    • The development of declarative memory in infants born preterm

      2010, Advances in Child Development and Behavior
      Citation Excerpt :

      These stressors can also affect brain development by altering the metabolism and thus, the function of the cells. The psychopathology associated with these factors includes mental retardation, hyperkinetic disorders, and significant emotional disturbance (for review, see Trask & Kosofsky, 2000). Although these factors have their most profound effect early in gestation, the older fetus is still vulnerable to maternally-transmitted infections and toxins.

    • Developmental Neurotoxicity

      2009, Clinical Neurotoxicology: Syndromes, Substances, Environments, Expert Consult - Online and Print
    • Developmental neurotoxicity

      2009, Clinical Neurotoxicology: Syndromes, Substances, Environments
    View all citing articles on Scopus

    Address reprint requests to Barry Kosofsky, MD, PhD, Laboratory of Molecular and, Developmental Neuroscience, Massachusetts General Hospital—East, 149 13th Street, Charlestown, MA 02129

    View full text