Acute occlusion of a major cerebral artery causes focal ischemia and ischemic edema. The ischemic event is progressive after the initial ictus in many patients with stroke. We hypothesize that ischemic edema adversely affects perfusion of the immediate and surrounding area. We further believe that that adverse effect is related to the development of focal tissue pressure gradients within brain parenchyma which further compromise already impaired perfusion. We propose to test the idea by studying the relationships of brain tissue pressue (TP), blood flow (rCBF), and brain water (BW) in three sets of experiments with cats that have undergone middle cerebral artery occlusion (MCAO). The first series of experiments focuses on how cellular volume and extracellular spaces change soon after the onset of ischemia and how those changes correlate with the development of focal TP gradients. Tissue impedance, resistance, and compliance measurements will demonstrate those volume changes while rCBF and TP are monitored simultaneously. The second set of studies involves better definition of cortical blood flow and TP thresholds that are associated with ischemic edema. The spectrum of edema, TP, and rCBF change that follow MCAO in the face of hyper and hypotension will be difined and their interrelationships clarified. The third set of experiments focuses on the effect of TP gradients upon rCBF by studying the distribution of ischemia over time after MCAO, and how the theoretical cycle of ischemia-edema-ischemia may develop. These studies should allow us to investigate the mechanisms by which ischemic edema develops and how in contributes to prolonged or progressive cerebral ischemia or both.
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