The blood-brain barrier: In vitro methods and toxicological applications

The blood-brain barrier (BBB) is reviewed with reference to in vitro cell culture models and their use and potential use in toxicological studies. The structure, function and in vitro study of brain microvessel endothelial cells (BMEC) is briefly described, as well as the effects of a number of xenobiotics, such as solvents, metals, polycations and herbicides, on the viability and barrier function of the BBB model. The biotransformation of xenobiotics is increasingly thought to be responsible for many toxic reactions seen in living systems. Few studies have addressed the effects of the products of biotransformation on the integrity of the barrier model. Many of the specific human bioactivating enzymes, such as cytochrome P-450s, can now be conveniently studied in eukaryotic in vitro gene expression systems. The combination of such systems with a well characterized porcine BMEC culture model might be useful in the study of reactive metabolites on the BBB, in terms of changes in indices of functional and structural BMEC viability. The potential applications and the value of such an experimental approach are discussed.