title: MicroRNA-132 attenuates neurobehavioral and neuropathological changes associated with intracerebral hemorrhage in mice.
abstract: Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yating
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Daojing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: hjw@tmu.edu.cn.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D016086:Lentivirus; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage* / Q000096:biosynthesis*
chemical_list: C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs
keywords: AChE; Inflammation; Intracerebral hemorrhage; Stroke; miR-132