Exercise Improves Recovery after Ischemic Brain Injury by Inducing the Expression of Angiopoietin-1 and Tie-2 in Rats

Abstract

Post-ischemia angiogenesis plays a critical part in the recovery of neural networks. Angiopoietin (Ang) has received much attention recently due to its key role in neurovascular remodeling. Exercise is proved to contribute to angiogenesis in normal or injured human skeletal muscle. The therapeutic effect of exercise on central angiogenesis after cerebral ischemia, however, has not been studied. In the present study, we investigated the relationship between exercise and the expression of Ang-1, Ang-2, and Tie-2 receptor tyrosine kinase in the brain using a rat model of stroke, with right middle cerebral artery occluded (MCAO). Male Sprague-Dawley rats were randomly grouped (n = 12): stroke-exercise (SE), stroke-no exercise (SNE) and sham-no exercise (SHAM). The SE group ran on a treadmill at a speed of 12 m/min, 30 min/day for 2 weeks. Functional recovery was assessed with neurological evaluation scores. Brain infarction was measured by Nissl staining. Expression of Ang-1, Ang-2, and Tie-2 were compared by immunohistochemical and real-time PCR analyses. The infarct volume in the SE group was significantly reduced compared with the SNE group (p < 0.05). Ang-1 (p < 0.05) and Tie-2 (p < 0.05) and their mRNA expression (p < 0.01 and p < 0.05, respectively) were increased in SE animals at 2 weeks, whereas Ang-2 expression remained unchanged. In conclusion, enhanced expression of Ang-1 and Tie-2 by exercise improves recovery of brain function in MCAO rats. Our results suggest the importance of angiogenesis in rehabilitation for post-ischemia brain injury and help to explain the underlying mechanism.