Enhanced apoptosis from early physical exercise rehabilitation following ischemic stroke

The effectiveness of the rehabilitative benefits of physical exercise appears to be contingent upon when the exercise is initiated after stroke. The present study assessed the hypothesis that very early exercise increases the extent of apoptotic cell death via increased expression of proapoptotic pr...

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Published inJournal of neuroscience research Vol. 95; no. 4; pp. 1017 - 1024
Main Authors Li, Fengwu, Shi, Wei, Zhao, Ethan Y., Geng, Xiaokun, Li, Xiaorong, Peng, Changya, Shen, Jiamei, Wang, Sainan, Ding, Yuchuan
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.04.2017
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Summary:The effectiveness of the rehabilitative benefits of physical exercise appears to be contingent upon when the exercise is initiated after stroke. The present study assessed the hypothesis that very early exercise increases the extent of apoptotic cell death via increased expression of proapoptotic proteins in a rat stroke model. Adult male Sprague‐Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 hr using an intraluminal filament and assigned to four nonexercise and three exercise groups. Exercise on a Rota‐Rod was initiated for 30 min at 6 hr (considered very early), at 24 hr (early), and at 3 days (relatively late) after reperfusion. At 24 hr after exercise, apoptotic cell death was determined. At 3 and 24 hr after exercise, the expression of pro‐ and antiapoptotic proteins was evaluated through Western blotting. As expected, ischemic stroke significantly increased the levels of apoptotic cell death. Compared with the stroke group without exercise, apoptotic cell death was further increased (P < 0.05) at 6 hr but not at 24 hr or 3 days with exercise. This exacerbated cell injury was associated with increased expression of proapoptotic proteins (BAX and caspase‐3). The expression of Bcl‐2, an antiapoptotic protein, was not affected by exercise. In ischemic stroke, apoptotic cell death was enhanced by very early exercise in association with increased expression of proapoptotic proteins. These results shed light on the time‐sensitive effect of exercise in poststroke rehabilitation. © 2016 Wiley Periodicals, Inc. Adult male Sprague‐Dawley rats were subjected to MCAO for 2 hr using an intraluminal filament and assigned to four nonexercise and three exercise groups. Exercise on a Rota‐Rod was initiated for 30 min at 6 hr (considered very early), at 24 hr (early), and at 3 days (relatively late) after reperfusion. At 24 hr after exercise, apoptotic cell death was determined. At 3 and 24 hr after exercise, the expression of pro‐ and antiapoptotic proteins was evaluated through Western blotting. Compared with the stroke group without exercise, apoptotic cell death was further increased (P < 0.05) at 6 hr but not at 24 hr or 3 days with exercise. This exacerbated cell injury was associated with increased expression of proapoptotic proteins (BAX and caspase‐3) and the ratio of BAX/Bcl‐2. The expression of Bcl‐2, an antiapoptotic protein, was not affected by exercise.
Bibliography:SIGNIFICANCE The use of exercise‐mediated adaptations to attenuate physical disability after stroke is an emerging arena in neurotherapeutics. However, fundamental questions regarding initiation time, which affect rehabilitation, remain unanswered. Although current guidelines recommend starting out‐of‐bed activity “early” during the acute phase of care, such guidelines do not specify how early exercise optimizes outcome. Our results shed light on the time‐sensitive effect of exercise in poststroke rehabilitation.
F. Li and W. Shi contributed equally to this work.
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ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.23890