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Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm.
Cerebrovascular Diseases Extra Pub Date : 2019-04-30 , DOI: 10.1159/000499077
Courtney L Fisher 1 , Stacie L Demel 2
Affiliation  

BACKGROUND Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. SUMMARY This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.

中文翻译:

非甾体类抗炎药:颅内动脉瘤的潜在药理治疗。

背景技术囊状颅内动脉瘤(IAs)是颅内动脉血管壁的外皮。IAs破裂导致蛛网膜下腔出血,这与高发病率和高死亡率有关。诸如修剪和卷取之类的外科手术具有相关的风险。当前,尚无行之有效的药物治疗可预防IAs的生长或破裂。响应于增加的壁切应力,促炎细胞因子的浸润是IA的标志。非甾体抗炎药(NSAIDs)正在被研究为通过抑制炎性途径减少IA的生长和/或预防IA的潜在治疗剂。发明内容该综述将讨论NSAID在减轻驱动IA进展和破裂的炎症中的作用。NSAID有两种主要的亚型,非选择性COX和选择性COX-2抑制剂,两者均具有治疗IA的优点。将提供证据表明NSAIDs抑制了与IA进展有关的几种关键炎症介质,包括核因子-κB,肿瘤坏死因子-α和基质金属蛋白酶。另外,将讨论NSAID在限制炎性细胞对内皮细胞的粘附和减弱内皮细胞衰老中的作用。重要信息:有大量的基础科学和临床前数据支持NSAID作为IA的有前途的治疗方法。另外,与单独使用阿司匹林或选择性COX-2抑制剂相比,低剂量阿司匹林与选择性COX-2抑制剂同时给予的联合治疗策略可能导致副作用降低。
更新日期:2019-11-01
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