Recent clinical data suggest that very early initiated physical rehabilitation (VEIPR) within 24 hours after stroke may reduce morbidity. However, there is limited evidence to support the beneficial effects of VEIPR and the underlying mechanisms are yet unknown. The present study investigated the effect of VEIPR on brain damage, inflammation, and neurobehavioral outcomes following cerebral ischemia. Rats that underwent transient focal cerebral ischemia (tFCI) were randomly assigned to VEIPR or non-exercise (NE) groups. VEIPR was induced 24 hours after the insult by initiating treadmill training for a maximum of 14 days while the NE group remained sedentary in their cages during this period. The results indicated that VEIPR significantly improved recovery of functional behavior as measured by neurological score, foot fault test, and Morris water maze performance. We also demonstrated that VEIPR significantly reduced infarct volume, brain water content, BBB damage, and acute inflammatory response. In summary, our results provide novel evidence that VEIPR confers marked neuroprotection against experimental stroke by attenuating pro-inflammatory reactions, brain edema, BBB damage, and cognitive and behavioral deficits.
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