Brain barrier systems: A new frontier in metal neurotoxicological research

Wei Zheng, Michael Aschner, Jean Francois Ghersi-Egea

Research output: Contribution to journalReview articlepeer-review

411 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalToxicology and Applied Pharmacology
Issue number1
StatePublished - Oct 1 2003
Externally publishedYes


  • Astrocytes
  • Blood-CSF barrier
  • Blood-brain barrier
  • Choroid plexus
  • Iron
  • Lead
  • Manganese
  • Mercury
  • Neurotoxicology
  • Toxicant
  • Transport

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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