Abstract TP350: Effects of Exercise Preconditioning on Promoting Endogenous Recovery Responses After Ischemic Stroke in Middle-Aged Mice

Background: Ischemic stroke, caused by the occlusion/stenosis of cerebral blood vessels, results in significant neurological damage. Evidence suggests that post-stroke rehabilitation with physical activity mitigates the effects of ischemic stroke. However, post-stroke neurological deficits make exercise challenging in the clinical setting. Despite increasing attention to the potential benefits of pre-stroke exercise, even in preclinical studies, its effects in middle-aged mice remain poorly understood. Aim: This study aimed to investigate the effects of treadmill exercise preconditioning on ischemic brain injury in middle-aged mice using the MCAO model. Methods: Early stages of middle-aged (8-month-old) male mice were assigned to sedentary or exercise groups. After 5 weeks of treadmill running (5 days per week after 1 week of acclimatization), mice underwent 45 minutes of MCAO and reperfusion. Behavioral assessments and body weight monitoring were performed before and after MCAO. Brain analyses for infarct volume and cellular responses were performed 14 days after stroke. Results: Fourteen days after stroke, lesion volume was significantly reduced in the exercise group compared to sedentary controls. Exercise preconditioning enhanced neurogenesis, angiogenesis, and oligodendrogenesis while suppressing reactive astrocyte activation. Improved neurological outcomes were also observed in the exercise group. Conclusions: Preconditioning with treadmill exercise provides neuroprotection against ischemic stroke by reducing infarct volume and promoting recovery. These findings suggest that daily exercise may be effective in reducing ischemic brain damage, even in middle-aged populations.