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.
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醋甲唑胺通过抑制蛛网膜下腔出血小鼠神经元凋亡改善神经行为
DOI：
10.1038/srep35055
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发表时间：
2016-10-12
影响因子：
4.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Li M;Wang W;Mai H;Zhang X;Wang J;Gao Y;Wang Y;Deng G;Gao L;Zhou S;Chen Q;Wang X
蛛网膜下腔出血(SAH)导致严重的神经功能障碍，如偏瘫、情绪障碍、认知和记忆障碍。目前，还没有明确的措施可以减少脑神经损伤。对SAH后脑神经保护的研究具有重要意义。本研究旨在探讨甲唑胺对C57BL/6J小鼠SAH动物模型和体外血液诱导的原代皮质神经元(PCNS)细胞模型的保护作用及其可能机制。我们证明，甲唑胺可以加速神经损伤的恢复，有效地缓解脑水肿，改善SAH小鼠的认知功能，并在血液或血红蛋白治疗的PCNS中提供神经保护，部分恢复正常的神经元形态。此外，免疫印迹分析显示，与赋形剂治疗的SAH小鼠相比，甲唑胺治疗的SAH小鼠的活性caspase-3的表达明显减少。此外，甲唑胺能有效地抑制血液暴露或血红蛋白损伤所诱导的PCNS中ROS的产生。但对SAH小鼠的死亡率、脑血流量波动、SAH分级及脑血管痉挛均无保护作用。由于甲唑胺是一种有效的碳酸酐酶抑制剂，可以穿透血脑屏障，并已在临床上用于治疗眼部疾病，因此有可能成为SAH的一种新疗法。
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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影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
1.7
作者：
Prunell, GF;Mathiesen, T;Svendgaard, NA
通讯作者：
Svendgaard, NA
影响因子：
4
作者：
Ke, Kaifu;Song, Yan;Cao, Maohong
通讯作者：
Cao, Maohong
影响因子：
4.8
作者：
Boet, R;Mee, E
通讯作者：
Mee, E
DOI：
10.7461/jcen.2014.16.3.193
发表时间：
2014-09
期刊：
Journal of cerebrovascular and endovascular neurosurgery
影响因子：
--
作者：
Park JH;Kim YI;Lim YC
通讯作者：
Lim YC