The interaction of intra-ischemic and postischemic events in the pathogenesis of ischemic brain injury will be studied in a model of diffuse, high-grade, reversible cerebral hemispheral ischemia in the awake rat. Ischemia will be produced in rats with prior occlusions of the vertebral arteries by bilateral common carotid artery occlusions. This insult produces coma and an isoelectric electroencephalogram in most animals. Removal of the carotid ligatures permits cerebral recirculation. Autoradiographic methods of local cerebral blood flow (14C-iodoantipyrine) and local cerebral glucose utilization (14C-2-deoxyglucose) will be employed. These data will be correlated with regional patterns of ATP and pH alterations and with regional NADH fluorescence, using topographic, pictorial methods. Regional assessments of glycolytic and energy metabolites, indices of free radical reactions, brain water and ion homeostasis, blood-brain barrier function, and histopathological alterations will be performed. The effects of preischemic glucose administration and of postischemic hypertension and hyperoxygenation on the severity of ischemic injury will be assessed. These studies will define regionally heterogeneous patterns of ischemic brain injury and will serve to clarify the contributions of events during ischemia and of postischemic factors in producing these lesions. The results will provide data on the basis of which future studies of the efficacy of therapeutic agents in ameliorating brain ischemia may be carried out.
