Brain Barrier Systems: a New Frontier in Metal Neurotoxicological Research

Overview

Journal Toxicol Appl Pharmacol

Specialties Pharmacology
Toxicology

Date 2003 Oct 14

PMID 14554098

Citations 128

Authors

Wei Zheng

Michael Aschner

Jean-Francois Ghersi-Egea

Affiliations

Soon will be listed here.

Abstract

The concept of brain barriers or a brain barrier system embraces the blood-brain interface, referred to as the blood-brain barrier, and the blood-cerebrospinal fluid (CSF) interface, referred to as the blood-CSF barrier. These brain barriers protect the CNS against chemical insults, by different complementary mechanisms. Toxic metal molecules can either bypass these mechanisms or be sequestered in and therefore potentially deleterious to brain barriers. Supportive evidence suggests that damage to blood-brain interfaces can lead to chemical-induced neurotoxicities. This review article examines the unique structure, specialization, and function of the brain barrier system, with particular emphasis on its toxicological implications. Typical examples of metal transport and toxicity at the barriers, such as lead (Pb), mercury (Hg), iron (Fe), and manganese (Mn), are discussed in detail with a special focus on the relevance to their toxic neurological consequences. Based on these discussions, the emerging research needs, such as construction of the new concept of blood-brain regional barriers, understanding of chemical effect on aged or immature barriers, and elucidation of the susceptibility of tight junctions to toxicants, are identified and addressed in this newly evolving field of neurotoxicology. They represent both clear challenges and fruitful research domains not only in neurotoxicology, but also in neurophysiology and pharmacology.

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