The specific aims of this project represent an attempt to quantitatively determine the inter-relationships among neuronal work, oxygen delivery and metabolism, and glucose delivery and metabolism in the rat brain during and after complete, reversible cerebral ischemia. Accomplishment of the aims will provide a basis for the description of the mechanisms which couple metabolism to function and how they are altered during and after stroke preventing full functional recovery. These goals will be reached through the use of reliable techniques and methodologies combining electrophysiological recording of brain activity, extracellular potassium and hydrogen ion activity, and tissue oxygen tension with optical monitoring of mitochondrial metabolism and intracellular pH by reflection spectrophotometry in situ under well controlled physiological and pathophysiological conditions. The data recorded from in vivo experiments will be compared directly with neurochemical correlates describing the metabolic state of the brain at significant times in the tissue response to stroke. The results from these proposed experiments will be directly applicable to the problem of brain dysfunction and recovery of function due to reversible or irreversible cell damage accompanying the imbalance between function and metabolism due to the pathophysiological stress which occurs during stroke. The uniqueness of this approach lies in the integration of various techniques which allow concurrent measurements of electrical brain activity, tissue oxygen content, cytochrome oxidase, potassium ion, hydrogen ion, and blood flow, volume and hemoglobin oxygenation; applied to the intact cerebral cortex in a manner which allows continuous determination in each rat during a variety of experimentally controlled conditions. This will allow specific analysis of the threat to continued normal brain function brought about by the failure of compensatory mechanisms which exist as a consequence of the total reliance of the brain on energy produced by oxygen metabolism.
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