Hyperglycemia and Oxidative Stress in the Human Brain With Diabetes

Cerebral GSH and Asc concentrations are modulated by increased oxidative stress induced by hyperglycemia in diabetes and reflect changes in the cerebral antioxidant defense system. Inhibition of cellular uptake of Asc by hyperglycemia further hampers maintaining adequate antioxidant capacities. Reduced concentrations of these antioxidants might serve as good indicators of increased susceptibility to oxidative damage, impaired cellular uptake or the antioxidant, and further, as sensitive in vivo biomarkers to assess early manifestations or progression of diabetic complications and the efficacy of the antioxidant therapy in the human brain. Specific aims (1) to determine cerebral concentrations of GSH and Asc in the living brain of healthy controls and type 2 diabetic patients; (2) to quantify the effect of chronic hyperglycemia on cellular uptake of Asc across the blood-brain barrier.