The barrier to diffusion and transport of substances from the blood into the brain is denoted the blood-brain barrier. The blood-brain barrier severely limits delivery to the brain of drugs that could be beneficial for treatment of central nervous system (CNS) diseases. Current methods for testing drug access to the brain are time consuming, imprecise, expensive and wasteful of laboratory animals. We propose to develop an in vitro model of the blood- brain barrier. It will be accomplished by developing methods to effectively co-culture the cells that form the blood-brain barrier, endothelial cells and astrocytes, in such a way as to simulate the environment of the brain and induce the barrier characteristics inherent to the capillaries there. The model will consist of a cellular monolayer connected by tight junctions on a permeable membrane of filter so that the barrier and transport properties can be completely characterized. The criteria for barrier formation will be based primarily on immunological characterization, electrical resistance measurements and transport studies. The in vitro model will allow one to readily assay the ability of drugs to cross the blood-brain barrier and will become a standard method for screening potential CNS therapeutics.
