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Downregulation of Microrna-421 Relieves Cerebral Ischemia/Reperfusion Injuries: Involvement of Anti-apoptotic and Antioxidant Activities

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Abstract

Reperfusion after cerebral ischemia causes additional ischemic injuries due to sudden recovery of blood supply. It usually produces excessive reactive species, mitochondrial dysfunction, oxidative stress, and cell apoptosis. Our study is designed to examine the role of miR-421 antagomir in cerebral ischemia/reperfusion injuries, as well as its underlying mechanisms. Middle cerebral artery occlusion (MCAO) model was performed with male Sprague Dawley (SD) rats for the initiation of cerebral ischemia/reperfusion injuries. Malondialdehyde (oxidative stress marker) and superoxide dismutase (antioxidant enzyme) were measured as indicators for oxidative stress. Flow cytometry was utilized to evaluate the cell apoptosis effects from miR-421. miR-421 antagomir significantly decreased neurological deficits and infarction volumes. It also downregulated malondialdehyde contents, upregulated superoxide dismutase activities, promoted the expressions of myeloid cells leukemia-1 and B cells lymphoma-2, and downregulated the expressions of Bax in the ischemic cortex. In addition, miR-421targeted MCL1 to exert its biological functions. Our study indicated the neuroprotection effects of miR-421 antagomir on cerebral I/R injuries, which involved the suppression of cell apoptosis and oxidative stress. MiR-421 might provide a new therapeutic direction for ischemia/reperfusion injuries.

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Authors and Affiliations

  1. Department of Neurology, Hebei General Hospital, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Yuehong Yue, Yang Zhang & Wanyi Wei

  2. Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Hongwei Zhao

  3. Department of Pharmacy, Hebei General Hospital, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Yuanyuan Yue

  4. Department of Neurology, Hebei General Hospital, No.348 Heping West Road, Xinhua district, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Yuehong Yue

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  1. Yuehong Yue
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  2. Hongwei Zhao
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  3. Yuanyuan Yue
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  4. Yang Zhang
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  5. Wanyi Wei
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Correspondence to Yuehong Yue.

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This study was approved by the Animal Ethics Committee of Hebei General Hospital. All procedures performed in studies involving animals were conducted the experiments according with the guidelines for the use of laboratory animals in China.

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Yue, Y., Zhao, H., Yue, Y. et al. Downregulation of Microrna-421 Relieves Cerebral Ischemia/Reperfusion Injuries: Involvement of Anti-apoptotic and Antioxidant Activities. Neuromol Med 22, 411–419 (2020). https://doi.org/10.1007/s12017-020-08600-8

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  • DOI: https://doi.org/10.1007/s12017-020-08600-8

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