title: Role of caveolin-1/vascular endothelial growth factor pathway in basic fibroblast growth factor-induced angiogenesis and neurogenesis after treadmill training following focal cerebral ischemia in rats.
abstract: Exercise is known to aid functional recovery following ischemia, though the mechanisms responsible for the beneficial effects of exercise on recovery from ischemic stroke are not fully understood. Basic fibroblast growth factor (bFGF) contributes to angiogenesis and promotes neurologic functional recovery after stroke. The present study aimed to investigate the possible mechanisms whereby treadmill exercise ameliorated impaired angiogenesis and neurogenesis following transient cerebral ischemia in middle cerebral artery occlusion (MCAO) rats. Treadmill exercise was started 2days after ischemia-reperfusion in MCAO rats and continued until 7 or 28days after MCAO, after which the animals were sacrificed. Changes in neurological deficit, infarction volume, neuronal morphology, expression levels of bFGF, caveolin-1, and vascular endothelial growth factor (VEGF), and angiogenesis and neurogenesis in the ischemic penumbra were examined by reverse transcription-polymerase chain reaction, western blots, and/or double immunofluorescence. The results suggested that treadmill exercise promoted the expression of bFGF, improved neurological recovery, and reduced infarct volume compared with non-exercised rats, and also enhanced the expression of caveolin-1, VEGF, VEGF receptor 2(FIK-1)/CD34, and Brdu/nestin staining. Small interfering RNA targeting bFGF blocked the protective effects of bFGF. In addition, 4weeks of post-stroke recovery still ameliorated ischemia-induced damage without bFGF shRNA. These findings suggest a novel mechanism underlying the beneficial effects of bFGF following stroke, and indicate that treadmill exercise may aid stroke recovery by regulating the caveolin-1/VEGF pathway in the ischemic zone.
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Qiongyi
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Huimei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Bai
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Yidian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Tu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuanxi Road, Wenzhou 325027, Zhejiang, China. Electronic address: chenxiangfey@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005080:Exercise Test / Q000379:methods; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008297:Male; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D051242:Caveolin 1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine
keywords: Angiogenesis; MCAO; Neurogenesis; Treadmill; bFGF; shRNA