Co-culture blood-brain barrier models and their use for pharmatoxicological screening.

ABSTRACT

The availability of an in vitro blood-brain barrier model would represent 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 microcapillary endothelial cells as well as several immortalized cell lines have been used to model the blood-brain barrier in vitro, partly in co-culture with astrocytes of various species, or various cell lines such as C6 glioma or N2a neuroblastoma cells. The collected data indicate that functional parameters often can be induced by soluble and membrane-bound factors in such cell systems. Relevant barrier-specific parameters are reviewed electrical resistance, and structure and function of the multidrug resistance P-glycoprotein and the y-glutamyl transpeptidase. Both P-glycoprotein and gamma-glutamyl transpeptidase have great influence on the pharmacodynamics, toxicology and metabolic capacity of the blood-brain barrier (drug efflux, oxidative damage, detoxification of endotoxins, etc.). Several available in vitro models appear to be suited for pharmacotoxicological screening, if the functional parameters gamma-glutamyl transpeptidase, P-glycoprotein as well as transendothelial resistance are monitored.