Effects of treadmill exercise on cerebral angiogenesis and MT1-MMP expression after cerebral ischemia in rats

Despite the increased understanding of treadmill training on angiogenesis of stroke patients, its mechanism is not clearly known. The metalloproteinase membrane type 1-metalloprotease (MT1-MMP) promotes the regeneration of the peripheral vessels but seldom research on the regeneration of cerebral blood vessels. This study was designed to investigate the effects of treadmill exercise on angiogenesis and MT1-MMP expression after cerebral ischemia in rats.

The adult male Sprague Dawley(SD) rats were randomly divided into three groups: sham operation group, the middle cerebral artery occlusion group(MCAO) and middle cerebral artery occlusion group(MCAO)+exercise group. In 4d, 7d or 14d after MCAO, respectively, the rats' neurological function was evaluated by the modified neurologic severity scores (mNSS); the microvessel numbers in areas surrounding cerebral ischemia were counted with Microvessel Density(MVD)analysis; the levels of MT1-MMP and reversion-inducing cysteine-rich protein with Kazalmotifs (RECK) were detected by Western-blot and immunohistochemical method.

Compared with MCAO group, the number of capillaries and the level of MT1-MMP expression around the area of cerebral ischemia were significantly increased in each exercise group (p < 0.05), while the level of RECK expression and the scores of mNSS in each exercise group were significantly decreased (p < 0.05).

This study suggested that treadmill exercise training can significantly promote angiogenesis and improve neurological function after cerebral ischemia. Its mechanism may be related to the upgraduation of the MT1-MMP expression in brain microvessels surrounding area of the ischemic rat.