title: MicroRNA-181c Exacerbates Brain Injury in Acute Ischemic Stroke.
abstract: 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 (H2O2) treatment inhibited BV2 microglia proliferation without inducing apoptosis, while miR-181c reduced proliferation but increased the apoptosis of these cells with or without LPS/H2O2treatment. LPS/H2O2induced 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.
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 2Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Ma
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 4Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 4Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tao
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 4Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Wang
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Han
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University.
authors.forename: Shubei
authors.initials: S
authors.lastname: Ma
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 3Beijing Institute for Brain Disorders; 4Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: 1Department of Neurology and Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University; 2Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
keywords: apoptosis; microRNA-181; microglia; neuron; stroke