COCULTURE BLOOD-BRAIN-BARRIER MODELS AND THEIR USE FOR PHARMATOXICOLOGICAL SCREENING

The availability of an in vitro blood-brain barrier model would repres ent a powerful alternative to experimental animals in pharmacological and toxicological research. This overview collects the various current approaches to build an in vitro model of the blood-brain barrier for these purposes. Purified bovine, porcine and human brain microcapillar y endothelial cells as well as several immortalized cell lines have be en used to model the blood-brain barrier in vitro, partly in co-cultur e with astrocytes of various species, or various cell lines such as C6 glioma or N2a neuroblastoma cells. The collected data indicate that f unctional parameters often can be induced by soluble and membrane-boun d factors in such cell systems. Relevant barrier-specific parameters a re reviewed: electrical resistance, and structure and function of the multidrug resistance P-glycoprotein and the gamma-glutamyl transpeptid ase. Both P-glycoprotein and gamma-glutamyl transpeptidase have great influence on the pharmacodynamics, toxicology and metabolic capacity o f the blood-brain barrier (drug efflux, oxidative damage, detoxificati on of endotoxins, etc.). Several available in vitro models appear to b e suited for pharmacotoxicological screening, if the functional parame ters gamma-glutamyl transpeptidase, P-glycoprotein as well as transend othelial resistance are monitored. (C) 1997 Published by Elsevier Scie nce Ltd.