Introduction: Accumulating evidence has shown that physical rehabilitation after stroke may reduce morbidity. The extents of these rehabilitative benefits, however, appear to be contingent upon the initiation time of exercise. The specific role of initiation time and the corresponding underlying mechanisms that influence the brain repair processes have yet to be thoroughly investigated. In this study, we assessed the hypothesis that very early exercise increases the risk of cell injury by stimulating lactic acidosis and ROS activation.
Methods: Using an intraluminal filament, adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion for 2 hours and were randomly assigned to 4 different training groups: 1) non-exercise, 2) Rota-rod exercise, initiated very early (at 6 h of reperfusion) for 30 min, 3) early (at 24 h), and 4) relatively late (at day 3) after stroke. The extent of brain injury was determined by apoptotic cell death 24 hours after exercise. Brain oxidative metabolism was determined by levels of NADH, ATP and reactive oxygen species (ROS) immediately after exercise, while lactic acidosis was also obtained at the same time point.
Results: Apoptotic cell death was significantly (p<0.05) increased in the 6 h but not 24 h exercise group compared to the stroke group without exercise. There was a decrease in apoptosis in the 3 day exercise group compared to the non-exercise stroke group (p<0.05). This exacerbated injury at the very early stage (6 h) was associated with increased lactate levels (p<0.05), although decreased levels (p<0.05) of NADH and ATP were observed in all exercise groups. ROS production was significantly enhanced by early but not late (3 days) exercise.
Conclusion: Lactic acidosis and ROS generation were enhanced by post-stroke exercise, if conducted too early. The early exercise may lose its benefits and diminish long-term functional recovery after stroke. Our results provide a basis for future investigation to reveal a more comprehensive understanding of the time-sensitive exercise effects in post-stroke rehabilitation, and aid clinicians in determining how best to administer exercise therapy post-stroke.