Blood-brain interfaces: relevance to cerebral drug metabolism

Toxicology Letters
J F Ghersi-EgeaJ D Fenstermacher

Abstract

The brain, with the exception of the circumventricular organs (CVOs), is partially protected from the invasion of blood-borne chemicals by the tight junctions that link adjacent cerebral endothelial cells and form the structural basis of the blood-brain barrier (BBB). In addition to the BBB, the epithelial layer of the choroid plexuses and the barrier layer of the arachnoid membrane complex comprise a second system for protecting the brain, a system often referred to as the blood-cerebrospinal fluid (CSF) barrier. In the past several years, several enzymes that are involved in hepatic drug metabolism have been found in the small microvessels from brain, the choroid plexuses, and the leptomeninges (pia plus arachnoid mater) as well as in some CVOs. These drug-metabolizing systems are inducible and may act at these various interfaces as 'enzymatic barriers' to influx. In particular, the activities of these enzymes in choroidal tissue are so high that the choroid plexuses can well be the major site of drug metabolism in the brain. The fate of intracerebrally formed polar metabolites and the potential of the blood-brain and blood-CSF barriers as sites for metabolic activation-induced neurotoxicity are discussed.

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Citations

Jul 20, 2005·Pharmaceutical Research·Conrad E JohansonAndrew Baird
Jun 30, 2012·Pharmaceutical Research·Christel A S BergströmJoseph A Nicolazzo
Apr 23, 2013·Clinical Pharmacokinetics·Antonello Di PaoloMario Del Tacca
Aug 6, 2003·Journal of Pharmaceutical and Biomedical Analysis·Daniela PopaElena Curea
Dec 5, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·P J Gaillard, A G de Boer
Oct 7, 2010·Pharmaceutical Research·Inge van RooyEnrico Mastrobattista
Sep 17, 2009·Seminars in Oncology·William R ShapiroWillem Boogerd
Nov 25, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bradley E Enerson, Lester R Drewes
May 27, 2016·Temperature : Multidisciplinary Biomedical Journal·Rika HosotaniKiyoshi Matsumura
Mar 16, 2006·The Journal of Pharmacy and Pharmacology·Joseph A NicolazzoWilliam N Charman
Jun 18, 2016·Drug Discovery Today·Chaitali GhoshDamir Janigro
Jan 3, 2001·Microscopy Research and Technique·J F Ghersi-Egea, N Strazielle
Feb 23, 2020·Critical Care Nursing Quarterly·Michael J ErdmanClay E Small
Dec 11, 2002·The Journal of Biological Chemistry·Hong ShenFrank C Brosius
Mar 21, 2019·Animal Models and Experimental Medicine·Thibaud ThiollierHugues Contamin
Aug 4, 2020·Acta neurologica Belgica·Megha Gautam, Ganesh Thapa
Nov 20, 2020·Fluids and Barriers of the CNS·Hossam KadryLuca Cucullo
Aug 10, 2021·Neurotoxicology·Daniela Silva-AdayaMaría E Gonsebatt

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