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

Abstract

IntroductionDespite 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.MethodsThe 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.ResultsCompared 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).ConclusionThis 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.

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

“…The therapeutic doses of physical exercise training used in our study were calculated as 40% of this maximum velocity in the case of mild exercise training, which amounted to approximately 15 m/min, and 80% in the case of intense exercise training, which was about 32 m/min (Zhang et al, 2012 ). To further increase the difference between our categories, we reduced speed in the mild group to a maximum of 12 m/min as previous studies (Tian et al, 2013 ; Zhang P. et al, 2013 ; Zhang et al, 2017 ; Tang et al, 2018 ). For the high-intensity group, we selected 30 m/min because we have employed this speed in previous work, in which we found that it reduced brain damage (Ding et al, 2006 ), blood-brain barrier dysfunction (Guo et al, 2008 ), and brain inflammation in stroke (Curry et al, 2010 ).…”

Buyang Huanwu Decoction Targets SIRT1/VEGF Pathway to Promote Angiogenesis After Cerebral Ischemia/Reperfusion Injury

“…Several vascular endothelial cell markers, such as CD31 (Chen et al, 2018), CD34 (Hu G.J. et al, 2017), and FVIII antigens (Tang et al, 2018), which stain both mature pre-existing vessels and newly formed blood vessels, have been utilized for the detection of MVD. In our study, MVD obtained by immunofluorescence staining of CD31.…”

Possible Neuroprotective Mechanisms of Physical Exercise in Neurodegeneration

“…PE can induce neuro-plastic changes in the human brain but with a wide inter-individual variability [ 17 ]. Regular PE is an effective autophagy inducer [ 33 ] and improves neurological function [ 12 ]. It also reduces chronic oxidative stress and promotes mitochondrial biogenesis.…”

“…For example, Lu et al examined the beneficial effect of treadmill exercise upon cognitive function in a streptozotocin (STZ)-induced AD rat model.Treadmill exercise significantly inhibited neuronal apoptosis in the rat hippocampal CA1 region [ 11 ]. Tang et al demonstrated treadmill exercise induced angiogenesis possibly by upregulating MT1-MMP expression, thereby providing protection against cerebral ischemia in rats [ 12 ]. Data from in vivo studies and human patients with neurodegeneration have proved that exercise improves cognitive performance [ 13 , 14 ].…”