Neuroprotection against transient cerebral ischemia by exercise pre-conditioning in rats

There is increasing evidence that physical activity is associated with decreased stroke risk and incidence. The purpose of this study was to determine whether increased levels of physical activity could reduce brain damage in rats subjected to transient or permanent middle cerebral artery (MCA) occlusion. Adult male Sprague-Dawley rats (three months old, n=36) exercised on a treadmill, which required repetitive locomotor movement, for 30 min each day for three weeks. Then, using an intraluminal filament, stroke was induced by either 2-h MCA occlusion followed by two days of reperfusion or by MCA occlusion for two days without reperfusion. Brain damage was determined by evaluating neurologic deficits and brain infarction. In rat with transient MCA occlusion, pre-ischemic motor activity significantly (p<0.01) reduced neurologic deficits and infarct volume in the frontoparietal cortex and the dorsolateral striatum. In contrast, the same exercise procedure did not produce neuroprotection in the permanently MCA-occluded stroke. In addition to decreasing stroke risk and incidence, physical activity also reduces brain damage after stroke. Although we cannot completely rule out a neuroprotective effect on ischemic episode, our study suggests that a major neuroprotection is conferred during reperfusion for rats that have undergone exercise pre-conditioning. This exercise-induced endogenous neuroprotection may be an effective strategy to ameliorate ischemia/reperfusion brain injury from stroke.