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RESEARCH ARTICLE
Year : 2022  |  Volume : 17  |  Issue : 8  |  Page : 1769-1775

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury


1 Central Laboratory, Renji Hospital; Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 Central Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
4 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
5 Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
6 Department of Neurosurgery, Changzheng Hospital, the Second Military Medical University, Shanghai, China

Correspondence Address:
Qi-Yong Mei
Department of Neurosurgery, Changzheng Hospital, the Second Military Medical University, Shanghai
China
Qin Hu
Central Laboratory, Renji Hospital; Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai
China
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Source of Support: This study was supported by the National Natural Science Foundation of China, Nos. 82071283 (to QH) and 81671130 (to QH); Medical Engineering Cross Research Foundation of Shanghai Jiao Tong University of China, No. YG2017MS83 (to QH); and from Shanghai Municipal Science and Technology Commission Medical Guidance Science and Technology Support Project of China, No. 19411968400 (to QYM), Conflict of Interest: None


DOI: 10.4103/1673-5374.332154

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Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1β. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.


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