In the coming years, the treatment of neurological disorders will be largely dependent on the development of new therapeutic agents and the modification of those compounds already in existence. The blood-brain barrier keeps most drugs out of the brain and severely limits their usefulness. Pharmaceutical companies will, therefore, need to screen many compounds for their entry into the brain and will also have to consider a variety of strategies designed to overcome the blood-brain barrier. Currently, compounds are screened by injecting them into large numbers of animals and either observing indirect and cumbersome and also raise important animal welfare concerns. A cell culture model of the blood-brain barrier would both facilitate rapid screening for compounds able to enter the brain and would also allow the systematic use of cell and molecular biological to enter the brain and would also allow the systematic use of cell and molecular biological techniques to develop drug delivery systems. In this proposal, we describe a technique for growing brain endothelial cells such that they form, the cell culture, an equivalent of the blood- brain barrier. We detail a set of experiments that will enable this model system to be used routinely by groups interested in nervous system therapeutics. We also describe ways in which this model system can be utilized to explore novel modes of drug delivery to the brain.
