Abstract TP193: The Protective Effects Of Exercise On Cerebral Ischemia Injury In Diabetes

Abstract

Ischemic stroke (IS) causes neurological dysfunction due to a loss of cerebral blood flow with exaggerated cerebral damage in diabetes. Exercise has shown beneficial effects on the vascular system and diabetes by mediating inter-organ communications. However, whether and how exercise contributes preventatively to the brain after IS in type 2 diabetes (T2D) is undefined. Here, we aimed to determine the effects of exercise on the metabolism, cerebral injury, neurological function, and protein expression in the brain after IS. T2D diabetic mice (db/db, 7-8 wks), and age/sex-matched controls (db/c) were subjected to exercise (10 m/min, 5 days/wk for 8-wks) or sedentary. Body weight and blood glucose were recorded once a week. One day after exercise, middle cerebral artery occlusion surgery was performed to induce IS. Sensorimotor deficits were assessed by the adhesive removal and corner tests two days after surgery. Afterward, the brain samples were collected for measuring the infarct size by cresyl violet staining. The proteins from the ipsilateral and contralateral brain were used for Western Blot to measure the levels of endothelial nitric oxide synthase (eNOS), neuronal NOS, NADPH oxidase (Nox2), Nox4, nuclear factor-kappa B (NF-κB), NF-κ light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα). We found: 1) exercise could stabilize the blood glucose in male db/db mice and have effects on preventing blood glucose increase at the early age of female db/db mice; 2) exercise could improve sensorimotor deficits by reducing tape contact and removal time and balancing the corner turning times (p< 0.05); 3) the infarct size is decreased in exercised group in both db/c (18.5 ± 2.2% and 22.2 ± 2.5%), and db/db mice (25.6 ± 3.1% and 35.6 ± 3.8%, exercise vs. sedentary, p< 0.05); 4) proteins related to oxidative stress and inflammation were downregulated in the brain of exercised diabetic IS mice. In conclusion, exercise could provide protective effects on stabilizing metabolism, improving neurological function, and reducing brain injury by downregulating the protein expression related to inflammation and oxidative stress in the brain.