This project is part of a continuing effort to identify factors influencing anoxic/ischemic brain damage and to evaluate methods of prophylaxis/treatment. We have demonstrated level of serum glucose concentration at exposure critically affects pathologic response to global ischemia. Further, we have clarified this effect operated by defining extent of lactic acid accumulation in brain: a link in the sequence of tissue changes damaging brain. Preliminary results with a model of focal cerebral ischemia involving permanent middle cerebral artery occlusion (MCA-O) show hyperglycemic cats show 4X larger infarcts and increased mortality from brain edema compared to normoglycemic cats. In addition to confirming these preliminary findings, we seek to investigate 2 further questions: 1) Does altering serum glucose concentration following MCA-O influence infarct size and mortality rate? This question is important in potentially affecting stroke management. 2) What are the mechanisms through which increased serum glucose concentrations at MCA-O cause larger infarcts? We will approach this last question using 2 approaches. The first will investigate topographic brain chemistry comparing intermediates of metabolism, adenine nucleotides and energy charge at different times after MCA-O at different brain sites in hyperglycemic and normoglycemic cats. These data will be correlated with each site's characteristics regarding infarct incidence as assessed from parallel pathologic studies. The second approach will investigate the temporal and spatial sequence of hemispheral tissue edema development using a) continuous tissue pressure measurements in the supply territory of the occluded MCA and b) tissue water content determinations in select brain regions at select times after MCA-O. Established techniques for surgery, physiologic monitoring, biochemical assays and water content determinations will be utilized while infarct size after long-term survival will be assessed using computer-assisted morphometry. Because many variables affect the consequences of cerebrovascular occlusion (occlusion site, collateral blood supply, duration of occlusion, perfusion pressure, blood viscosity, arterial blood PCO2, etc) we will control and/or measure these variables and use animal group sizes that permit statistical analyses to clarify serum glucose concentration's role. This study's findings potentially may influence stroke patients' care and hopefully may serve to reduce mortality and morbidity from cerebrovascular occlusion.