依达拉奉:一种新型自由基清除剂对脑血管损伤的神经保护作用

Hiroshi Yoshida, Hidekatsu Yanai, Yoshihisa Namiki, Kayoko Fukatsu-Sasaki, Nobuyuki Furutani, Norio Tada
{"title":"依达拉奉:一种新型自由基清除剂对脑血管损伤的神经保护作用","authors":"Hiroshi Yoshida,&nbsp;Hidekatsu Yanai,&nbsp;Yoshihisa Namiki,&nbsp;Kayoko Fukatsu-Sasaki,&nbsp;Nobuyuki Furutani,&nbsp;Norio Tada","doi":"10.1111/j.1527-3458.2006.00009.x","DOIUrl":null,"url":null,"abstract":"<p>Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post- reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus edaravone) is likely to target brain edema, reduce stroke death and improve the recovery from neurological deficits in stoke patients.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 1","pages":"9-20"},"PeriodicalIF":0.0000,"publicationDate":"2006-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00009.x","citationCount":"335","resultStr":"{\"title\":\"Neuroprotective Effects of Edaravone: a Novel Free Radical Scavenger in Cerebrovascular Injury\",\"authors\":\"Hiroshi Yoshida,&nbsp;Hidekatsu Yanai,&nbsp;Yoshihisa Namiki,&nbsp;Kayoko Fukatsu-Sasaki,&nbsp;Nobuyuki Furutani,&nbsp;Norio Tada\",\"doi\":\"10.1111/j.1527-3458.2006.00009.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post- reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus edaravone) is likely to target brain edema, reduce stroke death and improve the recovery from neurological deficits in stoke patients.</p>\",\"PeriodicalId\":94307,\"journal\":{\"name\":\"CNS drug reviews\",\"volume\":\"12 1\",\"pages\":\"9-20\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00009.x\",\"citationCount\":\"335\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drug reviews\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2006.00009.x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drug reviews","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2006.00009.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 335

摘要

再通和神经保护一直是急性缺血性脑卒中特异性治疗的主要目标。自由基在脑缺血损伤中起着至关重要的作用,自由基通过细胞膜不饱和脂肪酸的过氧化作用加重膜损伤,导致神经元死亡和脑水肿。自由基在脑卒中病理生理学中被认为是细胞损伤的关键因素。依达拉奉(3-甲基-1-苯基-2-吡唑啉-5- 1)是一种新型有效的自由基清除剂,已被临床用于减少缺血性中风后的神经元损伤。依达拉奉通过抑制内皮损伤和改善脑缺血时的神经元损伤发挥神经保护作用。依达拉奉提供了NOS的理想特征:增加eNOS(挽救缺血性卒中的有益NOS),降低nNOS和iNOS(有害NOS)。依达拉奉预处理可减少溶栓治疗引起的再灌注后脑水肿和出血事件。再灌注后大脑中超氧化物和一氧化氮的产生增加,再循环过程中氧自由基的激增与一氧化氮的增加导致过氧亚硝酸盐的形成,这是一种超强自由基。依达拉奉可以抑制氧化并增加eNOS表达引起的NO的产生,可能在再灌注时改善和保存脑血流量而不产生过氧亚硝酸盐。依达拉奉的临床经验表明,该药具有较宽的治疗时间窗。联合治疗(溶栓加依达拉奉)可能针对脑水肿,减少卒中死亡,并改善脑卒中患者神经功能障碍的恢复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Neuroprotective Effects of Edaravone: a Novel Free Radical Scavenger in Cerebrovascular Injury

Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post- reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus edaravone) is likely to target brain edema, reduce stroke death and improve the recovery from neurological deficits in stoke patients.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
ERRATUM Cortagine: Behavioral and Autonomic Function of the Selective CRF Receptor Subtype 1 Agonist Guanfacine and Guanfacine Extended Release: Treatment for ADHD and Related Disorders Pharmacology of the β-Carboline FG-7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects AUTHOR INDEX FOR VOLUME 13
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1