Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1/VEGF signaling pathways.

The purpose of this study was to investigate the role of caveolin-1 in treadmill-exercise-induced angiogenesis in the ischemic penumbra of rat brains, and whether caveolin-1 changes correlated with reduced brain injury induced by treadmill exercise, in rats after cerebral ischemia. Rats were randomized into five groups: sham-operated (S, n=7), model (M, n=36), exercise and model (EM, n=36), inhibitor and model (IM, n=36), and inhibitor, exercise, and model (IEM, n=36). Rats in the model groups underwent middle cerebral artery occlusion (MCAO). Rats in the inhibitor groups received an IP injection of the caveolin-1 inhibitor, daidzein (0.4 mg/kg), every 24 h following reperfusion. Rats were killed at 7 or 28 days after the operation. The exercise group showed better neurological recovery and smaller infarction volumes compared with the non-exercise group. Correspondingly, significant increases of caveolin-1 and vascular endothelial growth factor (VEGF) protein expression were observed compared with the non-exercise group. Additionally, the number of Flk-1/CD34 double-positive cells towards the ischemic penumbra was increased in the exercise group. Furthermore, the induction of VEGF protein, microvessel density, decrease of infarct volumes and neurological recovery was significantly inhibited by daidzein. This study indicates that treadmill exercise reduces brain injury in stroke. Our findings suggest that the caveolin-1 pathway is involved in the regulation of VEGF in association with promoted angiogenesis in the ischemic penumbra of rat brains after treadmill exercise. The caveolin-1/VEGF signaling pathway may be a potential target for therapeutic intervention in rats following MCAO.