Abstract Body: Background and rationale: Acute hyperglycemia caused by cerebral ischemia occurs when there is a lack of oxygen, resulting in anaerobic glycolysis. The Sirt1 and Sirt2 initiate the influence on glucose metabolism and cellular homeostasis through nucleocytoplasmic shuttling. We observed nuclear-cytoplasmic translocation of Sirt1 and Sirt2 during anaerobic glycolysis in the brain.
Methods: We investigated differences between young and aged mice in a non-fasting group of cerebral ischemia model. Young mice were subjected to time-dependently ischemia induction (0, 1, 2, or 3 h) without reperfusion, and aged mice underwent ischemia for 1 h. All mice measured relative cerebral blood flow using a Laser Doppler. To evaluate the cerebral cortex was separated from nuclear and cytoplasmic fractions by Western blotting.
Results: Aged mice had a more rapid and dramatic decrease in relative cerebral blood flow compared to young mice. Cytoplasmic-Sirt1 was elevated and cytoplasmic-Sirt2 did not change in young mice. In both young and aged mice in the ipsilateral cerebral cortex during 1 h ischemia, Sirt1 activity shifted from the nucleus to the cytoplasm, and Sirt2 activity shifted from the cytoplasm to the nucleus.
Conclusion: Cellular senescence can contribute to the accelerating glucose metabolism and aging processes in cerebral ischemia. We demonstrated that ischemia accelerates aging-like processes in the brain. These processes are mediated through the upregulation of the cytoplasmic-Sirt1 and nuclear-Sirt2 pathways.

Key words: Stroke, Ischemia, middle cerebral artery occlusion, nucleocytoplasmic shuttling, Sirt1, Sirt2