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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.

  • 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.


Several generalities that allow a basic understanding of the actions of neurotoxicants include (1) the privileged status of the nervous system (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.

Blood–Brain Barrier

The NS is protected from the adverse effects of many potential toxicants by an anatomical barrier between the blood and the brain, or a “blood–brain barrier” (BBB). 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. To gain entry to the NS, molecules must pass into the cell membranes of endothelial cells of the brain rather than between endothelial cells, as they do in other tissues (Figure 16–1). The principal basis of the blood–brain barrier is thought to be specialized endothelial cells in the brain’s microvasculature, aided, at least in part, by interactions with glia. In addition to this interface with blood, the brain, spinal cord, and peripheral nerves are also completely covered with a continuous lining of specialized cells that limits the entry of molecules from adjacent tissue. In the brain and spinal cord, this is the meningeal surface; in peripheral nerves, each fascicle of nerve is surrounded by perineurial cells. Among the unique properties of endothelial cells in the NS is the presence of tight junctions between cells. Thus, molecules must pass through membranes of endothelial cells, rather than between them, as they do in other tissues.


Schematic diagram of the blood–brain barrier. Systemic capillaries are depicted with intercellular gaps, or fenestrations, which permit ...

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