TY - JOUR
T1 - Brain barrier systems
T2 - A new frontier in metal neurotoxicological research
AU - Zheng, Wei
AU - Aschner, Michael
AU - Ghersi-Egea, Jean Francois
N1 - Funding Information:
This review was supported in part by grants from NIH/NIEHS (ES-08146 and ES-09089) and Johnson & Johnson Research Award to W.Z. and grants from NIH/NIEHS (ES-10563 and ES-07331) and Department of Defense (DAMD17-01-1-0685) awarded to M.A.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Blood-CSF barrier
KW - Blood-brain barrier
KW - Choroid plexus
KW - Iron
KW - Lead
KW - Manganese
KW - Mercury
KW - Neurotoxicology
KW - Toxicant
KW - Transport
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U2 - 10.1016/S0041-008X(03)00251-5
DO - 10.1016/S0041-008X(03)00251-5
M3 - Review article
C2 - 14554098
AN - SCOPUS:0141560468
SN - 0041-008X
VL - 192
SP - 1
EP - 11
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -