A Therapeutic Time Window & Dosage Of Early Exercise For Rats With Cerebral Ischemia

Background: Although evidence from prior animal and clinical studies indicated exercise is a safe, cost-effective post-stroke rehabilitative intervention, the proper combination of time-window and dosage of exercise for maximal functional recovery, and its underlying mechanisms, are still unknown. Purpose: We aimed to determine the optimal combination of exercise time-window and intensity by assessing mortality, neurological recovery, and underlying neurochemical mechanisms in MCAO rats. Methods: The study contained two parts: the time-window and the dosage experiments. In the time-window experiment, 8 different groups (exercise initiated 24hr, 48hr, 72hr, 96hr and its corresponding control), along with moderate intensity exercise, were assessed. In the dosage experiment, 3 different intensity exercise groups (Low, Moderate, High) were assessed. Mortality (only for the time-window experiment), infarct volume and neurological function (measured by modified Neurological Severity Score at 14 days) were the main outcomes measures. Results: In the time-window experiment, the mortality was the highest in the EXCISE 24h group (40%) than any of other three group ( p= 0.030, p= 0.030, p= 0.045 respectively). Additionally, infarct volumes were high and neurological function was poor. In the dosage experiment, the relative infarct volume of the Moderate (0.190±0.026, p < 0.01) was significantly smaller than the CON (0.318±0.035) and High (0.294±0.037) group, but no different than the Low group (0.188±0.012). Similarly, neurological function at 14 days was not different between Moderate and Low group although they both better than High and CON group. Moderate group was the most effective in reducing inflammation by decreasing IL-1β and TNF-α( p< 0.05, p< 0.05, respectively). Conclusions: Exercise initiated within 24 hours was neither safe or effective. Moderate intensity exercise initiated within 48 hours post-stroke apears to be an optimal combination for maximal post-stroke functional recovery.