Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model

Increasing evidence indicates that physical activity reduces brain damage after stroke. The purpose of this study was to determine whether exercise-induced neuroprotection is associated with improved brain integrity in stroke. Adult male Sprague-Dawley rats (3 months old, n=38) exercised on a treadmill, which required repetitive locomotor movement, for 30 minutes each day for 3 weeks. Then, using an intraluminal filament, stroke was induced by either 2 hours middle cerebral artery (MCA) occlusion followed by 24 or 48 hours of reperfusion. Brain damage was determined by evaluating brain infarction and brain edema, as well as ultrastructural alteration in endothelial-matrix-astrocyte interfaces. Pre-ischemic motor exercise significantly (p < 0.01) reduced infarct volume in the frontoparietal cortex and the dorsolateral striatum by 79%. By comparing the percentage difference in brain volume between the right (stroke site) and left hemispheres, we demonstrated a significant (p < 0.01) reduction in brain edema associated with reduced infarct volume in a 3 week exercise group (Group 1, n = 10) and a 3 week exercise plus 3 week rest group (Group 2, n = 10). Edema in cortex and striatum was 19 +/- 4% without exercise pre-conditioning (n = 10), in contrast to 5 +/- 3% (Group 1) or 6 +/- 4% (Group 2). The thickness of the basal lamina was enhanced by exercise. In ischemic rats without pre-exercise, alterations in microvessel ultrastructure with decreased luminal area, parenchymal edema and swollen astrocyte end-feet, as well as an abnormally thin basal lamina were observed. In contrast, exercise pre-conditioning significantly reduced the ischemic alterations, decreasing brain edema and increasing basal lamina thickness. This study suggests that exercise pre-conditioning reduces brain injury by decreasing cerebral permeability and enhancing brain integrity after stroke. This exercise-induced endogenous neuroprotection could be an effective strategy to ameliorate ischemic brain injury from stroke.