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OVERVIEW OF THE NERVOUS SYSTEM

Neurotoxicants and neurotoxins 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 neurotoxicants.

It is estimated that millions of people worldwide are exposed to known neurotoxicants each year, contributing to a dramatic increase over time of neurological diseases and associated deaths (Pritchard and Rosenorn-Lanng, 2015). An even larger potential problem stems from the incomplete information on many compounds that may have neurotoxic effects. The extent to which neurological disability may be related to chronic low-level chemical exposures is currently unknown; moreover, we do not understand the overall impact of environmental contaminants on brain function.

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.

Blood–Brain Barrier

The NS is protected from the adverse effects of many potential toxicants by a functional and anatomic barrier. In 1885, Ehrlich noticed that certain dyes did not distribute into the brain and spinal cord, whereas other tissues became stained. Conversely, when injected into the brain, the dye did not appear in the periphery. This observation pointed to the existence of an interface between the blood and the brain, or a “blood–brain barrier.” Most of the brain, spinal cord, retina, and peripheral NS (PNS) maintain this barrier with the blood, with selectivity similar to the interface between cells and the extracellular space. The principal basis of the blood–brain barrier is thought to be specialized endothelial cells ...

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