title: Exercise therapy augments the ischemia-induced proangiogenic state and results in sustained improvement after stroke.
abstract: The induction of angiogenesis will stimulate endogenous recovery mechanisms, which are involved in the long-term repair and restoration process of the brain after an ischemic event. Here, we tested whether exercise influences the pro-angiogenic factors and outcomes after cerebral infarction in rats. Wistar rats were exposed to two hours of middle-cerebral artery occlusion and reperfusion. Different durations of treadmill training were performed on the rats. The expression of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factor (VEGF)-related genes and proteins were higher over time post-ischemia, and exercise enhanced their expression. Sixteen days post-ischemia, the regional cerebral blood flow in the ischemic striatum was significantly increased in the running group over the sedentary. Although no difference was seen in infarct size between the running and sedentary groups, running evidently improved the neurobehavioral score. The effects of running on MMP2 expression, regional cerebral blood flow and outcome were abolished when animals were treated with bevacizumab (BEV), a VEGF-targeting antibody. Exercise therapy improves long-term stroke outcome by MMP2-VEGF-dependent mechanisms related to improved cerebral blood flow.
authors.affiliation: Department of Rehabilitation Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, China. yuewen_ma@126.com.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Qiang
authors.forename: Man
authors.initials: M
authors.lastname: He
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000068258:Bevacizumab; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology / Q000534:rehabilitation; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology; D018919:Neovascularization, Physiologic; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012420:Running; D020521:Stroke / Q000235:genetics / Q000503:physiopathology; D000071939:Stroke Rehabilitation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000068258:Bevacizumab; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat