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