Willed‑movement training reduces middle cerebral artery occlusion‑induced motor deficits and improves angiogenesis and survival of cerebral endothelial cells via upregulating hypoxia‑inducible factor‑1α

Zhou,Zhiwen; Ren,Xiang; Zhou,Wensheng; Zheng,Lijun

doi:10.3892/mmr.2019.10578

Willed‑movement training reduces middle cerebral artery occlusion‑induced motor deficits and improves angiogenesis and survival of cerebral endothelial cells via upregulating hypoxia‑inducible factor‑1α

Authors:
- Zhiwen Zhou
- Xiang Ren
- Wensheng Zhou
- Lijun Zheng
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Affiliations: Department of Neurology, Hunan Provincial People's Hospital, The First‑Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410016, P.R. China, Department of Rehabilitation, Hunan Provincial People's Hospital, The First‑Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410016, P.R. China
Published online on: August 9, 2019 https://doi.org/10.3892/mmr.2019.10578
Pages: 3910-3916

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Abstract

Willed movement facilitates neurological rehabilitation in patients with stroke. Focal ischaemia is the hallmark of patients after stroke, though the detailed molecular mechanism by which willed movement affects neurological rehabilitation after stroke is not fully understood. The aim of the present study was to dissect the key factors of the hypoxia signaling pathway responsible for the willed movement‑improved rehabilitation. Sprague‑Dawley rats undergoing right middle cerebral artery occlusion (MCAO) surgery were randomly divided into four groups: MCAO alone, willed movement (WM), environmental modification (EM) and common rehabilitation (CR). The neurological behaviour score was assessed, and infarction areas were detected by TTC staining. In addition, angiogenesis‑associated genes (vascular epithelial growth factor, angiogenin‑1, matrix metalloproteinases‑2 and ‑9) and hypoxia inducible factor (HIF)‑1α expression was investigated in cells derived from MCAO, WM, EM and CR groups. Finally, the role of HIF‑1α using HIF‑1α knockdown in HUVECs under hypoxic conditions was evaluated. WM significantly improved neurological behaviour and rehabilitation by increasing the behaviour score and by decreasing the infarction area. In addition, CR, EM and WM raised the expression of angiogenesis‑associated genes and HIF‑1α, thereby promoting in vitro tube formation of primary endothelial cells. Knockdown of HIF‑1α in HUVECs restored the increased expression of angiogenesis‑associated genes to normal levels and inhibited in vitro tube formation of HUVECs. Willed movement most effectively improved the neurological rehabilitation of rats with focal ischaemia through upregulation of HIF‑1α. The present findings provide insight into willed movement‑facilitated rehabilitation and may help treat stroke‑triggered motor deficit and improve angiogenesis of cerebral endothelial cells.

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