2. Academic Validation
  3. Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice

Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice

  • Sci Rep. 2016 Oct 12:6:35055. doi: 10.1038/srep35055.
Mingchang Li 1 2,  Wei Wang 1,  Haojian Mai 3,  Xinmu Zhang 2,  Jian Wang 2,  Yufeng Gao 4,  Yuefei Wang 1,  Gang Deng 1,  Ling Gao 5,  Shuanhu Zhou 6,  Qianxue Chen 1,  Xin Wang 2
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
  • 2 Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • 3 Department of Neurosurgery, Baoan District Hospital, Shenzhen, Guangdong, 518100, P. R. China.
  • 4 Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • 5 Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, P. R. China.
  • 6 Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
PMID: 27731352 DOI: 10.1038/srep35055
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.

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