The effect of voluntary exercise exposure on histological and neurobehavioral outcomes after ischemic brain injury in the rat.

Physical activity can induce neuroplastic adaptations and improve outcomes after cerebral injury. To determine if these outcomes are dependent on the type and timing of physical rehabilitation and the particular outcome/endpoint being tested, we evaluated the effect of voluntary exercise exposure beginning 24 h after cerebral ischemic injury on behavioral, physiological, and histological outcomes. In an observer-blinded fashion, Sprague-Dawley (300 g) male rats were allocated to three groups [sham-exercise (SHAM), stroke-exercise (SE), stroke-no exercise (SNE)] before a 1-h right middle cerebral artery occlusion (MCAo). Running wheels were used for voluntary exercise. A significant difference was found at 1 week post-infarction between the SNE and SE, with SNE showing worst neurological scores and higher number of foot faults. In addition, nearly 20% more of the SE animals regained their pre-MCAo weight by 7 days. These differences were not as evident at 2 weeks. No differences were found between the three groups in the paw preference test, wheel activity, and body temperature, as well as between SNE and SE with regards to infarct or hemispheric volumes, body weight, synaptophysin staining, and electroencephalography (EEG) testing. Within-group comparisons showed no relationships between infarct volume and foot faults, neurological scores, or exercise level. We conclude that (1) unlike behavioral outcomes, physiological and histological outcomes may not be influenced by the introduction of voluntary exercise once lesion maturation has occurred at 24 h, and (2) repetitive outcomes testing can obscure findings in rat models of cerebral ischemic injury.