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Dynamic Changes in miR-126 Expression in the Hippocampus and Penumbra Following Experimental Transient Global and Focal Cerebral Ischemia–Reperfusion

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Abstract

miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia–reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how miR-126 changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism miR-126 involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of miR-126-3p and miR-126-5p expression in mice and gerbils after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of miR-126-3p exacerbated the OGD/R-induced cell death and reduced cell viability. After miR-126-3p inhibition, the levels of SPRED1 and VEGFA expression were increased, and p-Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of miR-126-3p inhibition, we found that the expression of p-Raf-1 was significantly increased after the intervention of siSPRED1, while it was not statistically significant after intervention of siVEGFA. The reduction of miR-126 expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.

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Funding

This study was supported by Special Financial Grant from China Postdoctoral Science Foundation (2015T80592), General Financial Grant from China Postdoctoral Foundation (2014M561720), Key University Science Research Project of Jiangsu Province (16KJA310006), 2018 Medical Scientific Research Project of Jiangsu Provincial Health and Family Planning Commission (No. 141).

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  1. Zhanghong Xia and Li Wang have contributed equally to this article.

Authors and Affiliations

  1. Department of Neurology, Taizhou Second People’s Hospital, Taizhou, 225500, People’s Republic of China

    Zhang Hong Xiao, Ping Gan, Jing He & Li Dong Ding

  2. Department of Neurology, Affiliated Hospital, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Li Wang & Bing Chun Yan

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  1. Zhang Hong Xiao
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Correspondence to Bing Chun Yan or Li Dong Ding.

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Xiao, Z.H., Wang, L., Gan, P. et al. Dynamic Changes in miR-126 Expression in the Hippocampus and Penumbra Following Experimental Transient Global and Focal Cerebral Ischemia–Reperfusion. Neurochem Res 45, 1107–1119 (2020). https://doi.org/10.1007/s11064-020-02986-4

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