With the exception of aspirin in stroke prevention, no other therapeutic modalities have been proven to be efficacious in reducing ischemia-related brain damage or death using rigorously designed therapeutic protocols. Recent advances in the understanding of pathophysiology in cerebrovascular disease have generated enthusiasm in trials of new drugs. Clinical trials to confirm the therapeutic efficacy of new drugs in human stroke are costly, difficult to achieve and may involve risks for stroke victims. Preclinical trial using reliable animal models are desirable to preclude less promising drugs from entering the clinical trials. A focal ischemia model in the rat allowing objective and quantitative determination of infarct volume which varies with duration of ischemic insult will be established as an animal therapeutic model for ischemic stroke. Therapeutic protocol comparable to that of human trials will be applied to selected new drugs to determine their therapeutic efficacy. The overall objectives of this project are to establish a pharmacologically sound procedure to identify effective new drugs for future human trials in an economic and timely fashion.