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  • The central nervous system (CNS) is protected from the adverse effects of many potential toxicants by an anatomical blood–brain barrier and by the action of membrane transporters.

  • Neurons are highly dependent on aerobic metabolism because this energy is needed to maintain proper ion gradients.

  • Individual neurotoxic compounds typically target the neuron, the axon, the myelinating cell, or the neurotransmitter system.

  • Neuronopathy is the toxicant-induced irreversible loss of neurons, including its cytoplasmic extensions, dendrites and axons, and the myelin ensheathing the axon.

  • Neurotoxicants that cause axonopathies cause axonal degeneration, and loss of the myelin surrounding that axon; however, the neuron cell body remains intact.

  • Numerous naturally occurring toxins as well as synthetic chemicals may interrupt the transmission of impulses, block or accentuate transsynaptic communication, block reuptake of neurotransmitters, or interfere with second-messenger systems.


Many insights into the organization and function of the nervous system (NS) are based on observations derived from the action of neurotoxicants. Several general aspects modulate the NS response to chemicals, including (1) 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 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 specialized endothelial cells in the brain’s microvasculature, aided, in part, by interactions with glia. In addition to this interface with blood, the brain and spinal cord are covered with the meningeal surface and each fascicle of peripheral nerves is surrounded by perineurial cells. NS endothelial cells have tight junctions between cells. Thus, molecules must pass through membranes of endothelial cells, rather than between them, as they do in other tissues. The blood–brain barrier also contains transporters. If not actively transported into the brain, the penetration of toxicants is largely related to their lipid solubility and to their ability to pass through the plasma membranes of the cells forming the barrier. In the mature NS, the spinal and autonomic ganglia and other sites within the brain called circumventricular organs do not contain specialized endothelial tight junctions and are not protected by blood–tissue barriers. It is this cellular anatomical arrangement that allows the ...

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