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Effects of Treadmill Exercise on Motor and Cognitive Function Recovery of MCAO Mice Through the Caveolin-1/VEGF Signaling Pathway in Ischemic Penumbra

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Abstract

Exercise has been regarded as an effective rehabilitation strategy to facilitate motor and cognitive functional recovery after stroke, even though the complex effects associated with exercise-induced repair of cerebral ischemic injury are not fully elucidated. The enhancement of angiogenesis and neurogenesis, and the improvement of synaptic plasticity following moderate exercise are conducive to functional recovery after ischemic damage. Our previous studies have confirmed the angiogenesis and neurogenesis through the caveolin-1/VEGF pathway in MCAO rats. As an essential neurotrophic factor, BDNF has multiple effects on ischemic injury. In this study, we attempted to determine an additional mechanism of treadmill exercise-mediated motor and cognitive functional recovery through the caveolin-1/VEGF pathway associated with BDNF in the ischemic penumbra of MCAO mice. We found that mice exposed to treadmill exercise after the MCAO operation showed a significant up-regulation in expression of caveolin-1, VEGF, BDNF, synapsin I and CYFIP1 proteins, numbers of cells positive for BrdU/CD34, BDNF, BrdU/NeuN, BrdU/Synapsin I and CYFIP1 expression were increased, which support the reduction in neurological deficit and infarction volume, as well as improved synaptic morphology and spatial learning abilities, compared with the non-exercise mice. However, the caveolin-1 inhibitor, daidzein, resulted in increase in neurological deficit and infarction volume. The selective VEGFR2 inhibitor, PD173074, significantly induced larger infarction volume and neurological injury, and decreased the expression of BDNF in the ischemic penumbra. These findings indicate that exercise improves angiogenesis, neurogenesis and synaptic plasticity to ameliorate motor and cognitive impairment after stroke partially through the caveolin-1/VEGF pathway, which is associated with the coregulator factor, BDNF.

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Acknowledgements

This work was supported by The Natural Science Foundation of Zhejiang Province (No. Y12H170002) and Wenzhou Muni cipal Science and Technology Bureau (No. Y20170070). Moreover, we would like to express immense gratitude to the technical assistance of the Laboratory Animal Centre of Wenzhou Medical University and the Laboratory Centre of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou.

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  1. 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

    Zhenzhen Chen, Quan Hu, Qingfeng Xie, Shamin Wu, Qiongyi Pang, Meixia Liu, Yun Zhao, Fengxia Tu, Chan Liu & Xiang Chen

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Chen, Z., Hu, Q., Xie, Q. et al. Effects of Treadmill Exercise on Motor and Cognitive Function Recovery of MCAO Mice Through the Caveolin-1/VEGF Signaling Pathway in Ischemic Penumbra. Neurochem Res 44, 930–946 (2019). https://doi.org/10.1007/s11064-019-02728-1

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