Journal
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 30, Issue 3, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jstrokecerebrovasdis.2020.105485
Keywords
microRNA-181a-5p; Cerebral ischemic injury; Middle cerebral artery occlusion; Wnt/beta-catenin pathway; Oxygen-glucose-deprivation/reoxygenation; En2
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The study demonstrates the critical role of miR-181a-5p in cerebral ischemic injury by regulating En2 and the Wnt/β-catenin pathway to alleviate brain damage.
Purpose: Cerebral ischemic injury contributes to severe dysfunction of the brain, which triggers extremely high mortality and disability. The role of microRNA (miR)181a-5p is documented in cerebral ischemic injury. Therefore, this study intended to further figure out the mechanism of miR-181a-5p in cerebral ischemic injury. Methods: miR-181a-5p expression in middle cerebral artery occlusion (MCAO) mouse model, oxygen-glucose-deprivation/reoxygenation (OGD/R) N2a cell model, and serum from acute ischemic injury (ACI) patients was evaluated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-of-function assays were implemented in MCAO mice and OGD/R-induced N2a cells. In mice, the cerebral infarction area was assessed with 2,3,5-triphenyltetrazolium chloride staining, the number of damaged neurons by Nissl staining, and apoptosis by TdT-mediated dUTP-biotin nick end-labeling staining. Moreover, N2a cell apoptosis and proliferation were determined with flow cytometry or 5-ethynyl-2'-deoxyuridine staining, respectively. The expression of En2 and Wnt/b-catenin pathway-related factors was determined with RT-qPCR and Western blot analysis. The targeting relationship between miR-181a-5p and En2 was evaluated by dual luciferase reporter gene assay. Results: miR-181a-5p was highly expressed in serum of ACI patients, MCAO mice, and OGD/R-induced N2a cells. En2, lowly expressed in MCAO mice, was targeted by miR-181a-5p, and miR-181a-5p down-regulation activated the Wnt/ b-catenin pathway. Furthermore, miR-181a-5p inhibition or En2 overexpression reduced cerebral infarction area, the number of damaged neurons, and apoptosis in MCAO mice, and also diminished apoptosis and accelerated proliferation of OGD/ R-induced N2a cells. Conclusion: miR-181a-5p suppression activated Wnt/b-catenin
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