MicroRNA-181c Exacerbates Brain Injury in Acute Ischemic Stroke

• Published in: Aging and disease 2016-12, Vol.7 (6), p.705-714
• Main Authors: Ma, Qingfeng, Zhao, Haiping, Tao, Zhen, Wang, Rongliang, Liu, Ping, Han, Ziping, Ma, Shubei, Luo, Yumin, Jia, Jianping
• Format: Article
• Language: English
• Subjects: Apoptosis; Brain damage; Brain injuries; Causes of; Cerebral ischemia; Complications and side effects; Development and progression; Genetic aspects; Health aspects; Hydrogen peroxide; Inflammation; Ischemia; Lymphocytes; Lymphomas; MicroRNA; Mitogens; Neurons; Original; Oxidative stress; Peroxides; Physiological aspects; Proteins; Stroke; Stroke patients; Tumors
• ISSN: 2152-5250; 2152-5250
• DOI: 10.14336/ad.2016.0320

MicroRNA-181 (miR-181) is highly expressed in the brain, and downregulated in miRNA expression profiles of acute ischemic stroke patients. However, the roles of miR-181c in stroke are not known. The clinical relevance of miR-181c in acute stroke patients was evaluated by real-time PCR and correlation analyses. Proliferation and apoptosis of BV2 microglial cells and Neuro-2a cells cultured separately or together under oxidative stress or inflammation were assessed with the Cell Counting Kit-8 and by flow cytometry, respectively. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in C57/BL6 mice, and cerebral infarct volume, microglia activation, and expression of pro-apoptotic factors were evaluated by 2,3,5-triphenyl-2H-tetrazolium chloride staining, immunocytochemistry, and western blotting, respectively. Plasma levels of miR-181c were decreased in stroke patients relative to healthy individuals, and were positively correlated with neutrophil number and blood platelet count and negatively correlated with lymphocyte number. Lipopolysaccharide (LPS)/hydrogen peroxide (H O ) treatment inhibited BV2 microglia proliferation without inducing apoptosis, while miR-181c reduced proliferation but increased the apoptosis of these cells with or without LPS/H O treatment. LPS/H O induced apoptosis in Neuro-2a cells co-cultured with BV2 cells, an effect that was potentiated by miR-181c. In the MCAO model, miR-181c agomir modestly increased infarct volume, markedly decreased microglia activation and B cell lymphoma-2 expression, and increased the levels of pro-apoptotic proteins in the ischemic brain. Our data indicate that miR-181c contributes to brain injury in acute ischemic stroke by promoting apoptosis of microglia and neurons via modulation of pro- and anti-apoptotic proteins.