Reperfusion of ischemic tissues is presently thought to be potentially useful in the treatment of focal stroke. Pharmacologically or surgically- reflow, however, might trigger another series of events more deleterious than those for persisting ischemia. The overall Objective of this proposal is to determine the benefits of reperfusion as a function of ischemic duration and proximity of the tissue to the ischemic focus. The rat model of temporary middle cerebral artery (MCA) occlusion emulates the clinical manifestations of focal stroke and is amenable to Studies which will evaluate the viability of the focal and perifocal regions during reperfusion after increasing periods of ischemia. Such studies will delineate the time threshold for irreversible damage not only in the ischemic core, but also in the perifocal region. The focus of these studies is to evaluate the metabolic viability of the affected regions after varying periods of ischemia. Experience has shown that the different regions of the brain affected by MCA occlusion are relatively small. Microquantitative histochemistry resolves this problem by increasing our sampling precision of the perifocal, focal and normal tissue regions. Such a strategy, however, requires supporting techniques to identify the regions of interest and to that end, autoradiograms from quantitative cerebral blood flow measurements are a guide to the dissection of lyophilized tissue. Administration of 14C-2-Deoxyglucose during ischemia delineates the site of the original ischemic focus. Routine histological studies are planned and electrophysiology performed when required to compliment the metabolic data. Preliminary studies with proton MRI indicate that this non-invasive procedure provides a natural history of edema formation and resolution, and the metabolic correlates to these changes will be determined. The clinical management of an acute ischemic insult to the brain remains problematic. Until the events leading up to death or infarction are established in focal ischemia, little insight can be gained on how to improve therapy. The proposed study will provide new information on the recovery process in the focal and perifocal regions, if they differ and whether unique forms of intervention should be tried to improve the safety of reperfusion.