Abstract TP260: Early Voluntary But Not Forced Exercise Improve Neural Remodeling After Cerebral Ischemia By Promotingmitochondrial Transport

Abstract

Introduction: Neural remodeling occurs in the early stage after cerebral ischemia, and rehabilitation training promotes the recovery of neronal function to the greatest extent. Although the forced exercise within 6 hours after cerebral ischemia effectively promote long-term nerve remodeling, it enhanced the short-term ischemic injury. Instead, early voluntary exercise is relatively safe. The present study determined whether early voluntary exercise safely and effectively promote long-term functional recovery after stroke. Methods: A total of 60 adult male Sprague-Dawley rats were divided into 4 groups: 1) sham control, 2) stroke, 3) stroke with forced exercise from 6 hours to 28 days (30min every day), 4) stroke with voluntary exercise from 6 h to 28 d. Infarct volume and neurological deficit were evaluated. Long-term functional outcomes were determined by grid walk, rota-rod, adhesive tape touch, and Morris water maze. Levels of mRNA and proteins of neuroplasticity and synaptogenesis were determined by real-time PCR and Western blot. After 28 days of reperfusion, the rats were taken for measured with electron microscopy. Results . 1. Early forced exercise aggravated cerebral infarction, while early voluntary exercise reduced infarct volume. 2. As compared to forced exercise, voluntary exercise improved running time in rota-rod, shortened the time of removing adhesive tape and reduced the time of finding platform in water maze. 3. Voluntary exercise significantly stimulated production of irisin to brain and growth differentiation factor 10 (GDF10), suggesting voluntary exercise improve long-term function through release of GDF10. 4. Voluntary exercise promoted synaptophysin, brain-derived neurotrophic factorand postsynaptic density protein-95 expression, suggesting voluntary exercise improved neuroplastic and synaptogenic. 5. Electron microscopy showed that voluntary effectively improved the ultrastructure of mitochondria(32±3.1%) after stroke, alleviated swelling of mitochondria (20±2.5%). Conclusions: Voluntary exercise may become effective rehabilitation strategy, which not only induced short term neuroprotection by reducing infarct volume, but also promoted the long-term functional recovery after stroke.