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  • Overview of the Nervous System

    • Blood–Brain Barrier

    • Energy Requirements

    • Axonal Transport

    • Axonal Degeneration

    • Myelin Formation and Maintenance

    • Neurotransmission

    • Development of the Nervous System

    • Environmental Factors Relevant to Neurodegenerative Diseases

  • Functional Manifestations of Neurotoxicity

  • Mechanisms of Neurotoxicity

    • Neuronopathies

      • Doxorubicin

      • Methyl Mercury

      • Trimethyltin

    • Axonopathies

      • Gamma-Diketones

      • Carbon Disulfide

      • β,β′-Iminodipropionitrile

      • Acrylamide

      • Organophosphorus Compounds

      • Pyridinethione

      • Microtubule-Associated Neurotoxicity

    • Myelinopathies

      • Hexachlorophene

      • Tellurium

      • Lead

    • Astrocytes

      • Ammonia

      • Nitrochemicals

      • Methionine Sulfoximine

      • Fluroacetate and Fluorocitrate

    • Neurotransmission-Associated Neurotoxicity

      • Nicotine

      • Cocaine and Amphetamines

      • Excitatory Amino Acids

    • Models of Neurodegenerative Disease

      • 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine

      • Manganese

      • Guamanian Cycad-Induced Parkinsonism/Amyotrophic Lateral Sclerosis Syndrome

    • Developmentally Neurotoxic Chemicals

  • Chemicals That Induce Depression of Nervous System Function

  • In Vitro and Other Alternative Approaches to Neurotoxicology

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Overview of the Nervous System

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Neurotoxicants and toxins have been extensively studied because of their toxic effects on humans and their utility in the study of the nervous system (NS). Many insights into the organization and function of the NS are based on observations derived from the action of neurotoxicants. The binding of exogenous compounds to membranes has been the basis for the definition of specific receptors within the brain; an understanding of the roles of different cell types in the function of the NS has stemmed from the selectivity of certain toxicants in injuring specific cell types while sparing others, and important differences in basic metabolic requirements of different subpopulations of neurons have been inferred from the effects of toxicants.

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It is estimated that millions of people worldwide are exposed to known neurotoxicants each year, a fact underscored by repeated outbreaks of neurological disease (Federal Register, 1994). An even larger potential problem stems from the incomplete information on many compounds that may have neurotoxic effects. Unknown is the extent to which neurological disability maybe related to chronic low-level exposures, nor do we understand the overall impact of environmental contaminants on brain function.

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In order to study neurotoxicological consequences of chemical exposures, one must understand the structure, function, and development of the NS. These features can be quite complex, with differential anatomy, physiology, and cell types specific for location and function. Several general aspects modulate the NS response to chemicals, including (1) the privileged status of the NS with the maintenance of a biochemical barrier between the brain and the blood, (2) the importance of the high energy requirements of the brain, (3) the spatial extensions of the NS as long cellular processes and the requirements of cells with such a complex geometry, (4) the maintenance of an environment rich in lipids, (5) the transmission of information across extracellular space at the synapse, (6) the distances over which electrical impulses must be transmitted, coordinated, and integrated, and (7) development and regenerative patterns of the NS. Each of these features of the NS carries with it specialized metabolic/physiological requirements and unique vulnerabilities to toxic compounds.

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Blood–Brain Barrier

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The NS is protected from the adverse effects of many potential toxicants by an anatomic barrier. In ...

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