title: Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice.
abstract: Subarachnoid hemorrhage (SAH) results in significant nerve dysfunction, such as hemiplegia, mood disorders, cognitive and memory impairment. Currently, no clear measures can reduce brain nerve damage. The study of brain nerve protection after SAH is of great significance. We aim to evaluate the protective effects and the possible mechanism of methazolamide in C57BL/6J SAH animal model in vivo and in blood-induced primary cortical neuron (PCNs) cellular model of SAH in vitro. We demonstrate that methazolamide accelerates the recovery of neurological damage, effectively relieves cerebral edema, and improves cognitive function in SAH mice as well as offers neuroprotection in blood- or hemoglobin-treated PCNs and partially restores normal neuronal morphology. In addition, western blot analyses show obviously decreased expression of active caspase-3 in methazolamide-treated SAH mice comparing with vehicle-treated SAH animals. Furthermore, methazolamide effectively inhibits ROS production in PCNs induced by blood exposure or hemoglobin insult. However, methazolamide has no protective effects in morality, fluctuation of cerebral blood flow, SAH grade, and cerebral vasospasm of SAH mice. Given methazolamide, a potent carbonic anhydrase inhibitor, can penetrate the blood-brain barrier and has been used in clinic in the treatment of ocular conditions, it provides potential as a novel therapy for SAH.
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.|Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Mingchang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Baoan District Hospital, Shenzhen, Guangdong, 518100, P. R. China.
authors.forename: Haojian
authors.initials: H
authors.lastname: Mai
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Xinmu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Deng
authors.affiliation: Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
authors.forename: Qianxue
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008704:Methazolamide / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism; D020301:Vasospasm, Intracranial
chemical_list: D017382:Reactive Oxygen Species; D053148:Caspase 3; D008704:Methazolamide