ABSTRACT

Neuroprotective drugs, while promising in experimental models, have nearly all failed in clinical trials. The successful translation of clinical trials from preclinical research to clinical trials has demonstrated that stroke is a treatable disorder in the hyperacute stage. To serve as the midwife for the translation of a stroke therapeutic from preclinical program to successful trial, one must understand previous failures. If reversible ischemic tissue is not present at the time of treatment, then neuroprotective therapy cannot be expected to work. Studies in animals have relied on infarct size, measured early, to judge therapeutic efficacy, whereas clinical trials have relied on behavioral outcomes, measured some time after stroke. As some scientists have emphasized, the target of neuroprotective therapy is the penumbra, ischemic tissue that surrounds the infarct core and is functionally impaired but with damage that is potentially reversible.