Abstract Body: Background and rationale: Glucose is the most important metabolic fuel for the brain. Acute hyperglycemia due to cerebral ischemia causes mitochondrial dysfunction and slows cell cycle progression, resulting in oxidative stress and cell proliferation inhibition. Glycolysis usually occurs in the cytoplasm during ischemia. The mechanism of cerebral ischemia-induced hyperglycemia was investigated.
Methods: Both non-fasting young (2-month-old) and aged (18-month-old) mice were subjected to middle cerebral artery occlusion (MCAO) for 1, 2 or 3 hours without reperfusion. Relative cerebral blood flow was measured by Laser Doppler and peripheral blood glucose was measured by glucometer after induction of MCAO at various time points. The ipsilateral cerebral cortex tissue of the brain was harvested. Total cellular protein and protein in cytoplasmic fraction was prepared and analyzed by western blot.
Results: In both young and aged mice, MCAO induced hyperglycemic condition as peripheral blood glucose levels were increased in MCAO mice compared to non-MCAO (sham) mice. Relative cerebral blood flow was decreased during the course of MCAO, indicating ischemia status. In ipsilateral cerebral cortex tissue, phosphorylated (Ser1177) endothelial nitric oxide synthase (eNOS) levels were decreased in total protein and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) levels were increased in cytoplasmic fraction in a MCAO-time dependent manner.
Conclusion: Ischemia induced hyperglycemia condition in both young and aged mice. In the ischemia brain, levels of phosphorylated eNOS were decreased, whereas the levels of GAPDH were increased. Taken together, these data suggest that MCAO induces hyperglycemia via enhancing glycolysis in the brain.

Key words: Stroke, Ischemia, middle cerebral artery occlusion, glycolysis, glycolytic enzyme, GAPDH, eNOS