title: The mechanisms of neurotoxicity and the selective vulnerability of nervous system sites.
abstract: The spatial heterogeneity of the structure, function, and cellular composition of the nervous system confers extraordinary complexity and a multiplicity of mechanisms of chemical neurotoxicity. Because of its relatively high metabolic demands and functional dependence on postmitotic neurons, the nervous system is vulnerable to a variety of xenobiotics that affect essential homeostatic mechanisms that support function. Despite protection from the neuroglia and blood-brain barrier, the central nervous system is prone to attack from lipophilic toxicants and those that hijack endogenous transport, receptor, metabolic, and other biochemical systems. The inherent predilection of chemicals for highly conserved biochemical systems confers selective vulnerability of the nervous system to neurotoxicants. This chapter discusses selective vulnerability of the nervous system in the context of neuron-specific decrements (axonopathy, myelinopathy, disruption of neurotransmission), and the degree to which neuronal damage is facilitated or ameliorated by surrounding nonneural cells in both the central and peripheral nervous systems.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, NC, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Maurer
authors.affiliation: Toxicology Program, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address: philbert@umich.edu.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Philbert
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D004198:Disease Susceptibility; D006801:Humans; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009435:Synaptic Transmission / Q000502:physiology
keywords: Schwann cells; astrocytes; axonopathy; blood–brain barrier; central nervous system; microglia; myelinopathy; neurotoxicants; neurotransmission; peripheral nervous system