title: Treadmill Exercise Promotes Neurogenesis in Ischemic Rat Brains via Caveolin-1/VEGF Signaling Pathways.
abstract: Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2'-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation.
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital, 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 of Wenzhou Medical University and Yuying Children's Hospital, 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 of Wenzhou Medical University and Yuying Children's Hospital, No. 109, Xueyuanxi Road, Wenzhou, 325027, Zhejiang, China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Liu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital, No. 109, Xueyuanxi Road, Wenzhou, 325027, Zhejiang, China.
authors.forename: Jingzi
authors.initials: J
authors.lastname: Pan
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital, No. 109, Xueyuanxi Road, Wenzhou, 325027, Zhejiang, China.
authors.forename: Bingwu
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital, No. 109, Xueyuanxi Road, Wenzhou, 325027, Zhejiang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital, 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 of Wenzhou Medical University and Yuying Children's Hospital, 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 of Wenzhou Medical University and Yuying Children's Hospital, No. 109, Xueyuanxi Road, Wenzhou, 325027, Zhejiang, China. chenxianghn2006@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000502:physiology; D000089662:Doublecortin Protein; D005080:Exercise Test / Q000379:methods; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Caveolin-1; MCAO; Neural stem/progenitor cell; Subventricular zone; Treadmill; VEGF