BLOOD-BRAIN INTERFACES - RELEVANCE TO CEREBRAL DRUG-METABOLISM

The brain, with the exception of the circumventricular organs (CVOs), is partially protected from the invasion of blood-borne chemicals by t he tight junctions that link adjacent cerebral endothelial cells and f orm the structural basis of the blood-brain barrier (BBB). In addition to the BBB, the epithelial layer of the choroid plexuses and the barr ier layer of the arachnoid membrane complex comprise a second system f or protecting the brain, a system often referred to as the blood-cereb rospinal fluid (CSF) barrier. In the past several years, several enzym es that are involved in hepatic drug metabolism have been found in the small microvessels from brain, the choroid plexuses, and the leptomen inges (pia plus arachnoid mater) as well as in some CVOs. These drug-m etabolizing systems are inducible and may act at these various interfa ces as 'enzymatic barriers' to influx. In particular, the activities o f these enzymes in choroidal tissue are so high that the choroid plexu ses can well be the major site of drug metabolism in the brain. The fa te of intracerebrally formed polar metabolites and the potential of th e blood-brain and blood-CSF barriers as sites for metabolic activation -induced neurotoxicity are discussed.