The proposed studies addresses the following question: does dexamethasone influence stroke injury by altering brain glucose transport or microvascular fuel metabolism? Dexamethasone treatment can markedly worsen stroke damage in rats and has variable efficacy in ameliorating human stroke damage. We plan to employ DEX as a tool to study regulation of glucose entry into brain. It may augment ischemic damage by causing both hyperglycemia and hyperinsulinemia, conditions common in Type II diabetes. Glucose becomes toxic during stroke by increasing brain lactic acid levels. Thus, both hyperglycemia and induction of brain hexose transport may aggravate stroke-related cerebral lactic acidosis. Altered energy metabolism by the brain's microvasculature may also influence stroke damage through vascular dysfunction. Novel causes for dexamethasone-dependent stroke injury are to be tested, based on three proposed hypotheses: 1) Chronic dexamethasone administration modifies blood-brain glucose transport; 2) Dexamethasone also alters glucose transport by brain parenchymal cells; and 3) Exposure of brain microvessels to dexamethasone may impair brain microvessel energy metabolism. Each of these hypotheses pertains to altered tolerance to cerebral ischemia. To evaluate these hypotheses, studies will be performed with the following aims: 1) Determine the influence of dexamethasone on brain hexose transport in vivo; 2) Characterize hexose transport by brain microvessels and parenchyma in vitro after dexamethasone exposure; 3) Evaluate possible molecular mechanisms whereby dexamethasone modulates glucose transport; 4) Determine whether dexamethasone changes fuel metabolism in the brain microvasculature in a manner which lessens tolerance to ischemia or fuel deprivation.