The science of cerebral ischemia and the quest for neuroprotection: navigating past failure to future success.
The science of cerebral ischemia and the quest for neuroprotection: navigating past failure to future success.
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DOI：
10.3171/2012.11.jns12408
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发表时间：
2013-05
影响因子：
4.1
通讯作者：
Huber JD
中科院分区：
文献类型：
--
作者：
Turner RC;Dodson SC;Rosen CL;Huber JD
缺血性卒中仍然是发病和死亡的主要原因，可供选择的治疗方法很少。神经保护剂的发展，一个曾经有前途的研究领域，未能成功地从实验室转化到床边。这项工作回顾了缺血级联，级联中的代理目标步骤，以及缺乏翻译的潜在原因。额外的治疗目标突出，需要进一步调查的领域进行了讨论。很明显，需要追求替代目标，例如神经胶质细胞在神经损伤和恢复中的作用，特别是神经元，星形胶质细胞，小胶质细胞和血管系统之间的相互作用。类似地，许多信号分子如基质金属蛋白酶和高迁移率族蛋白1蛋白的双相性质必须进一步研究，以阐明有害与有益活性的时期。
Ischemic stroke remains a leading cause of morbidity and death for which few therapeutic options are available. The development of neuroprotective agents, a once promising field of investigation, has failed to translate from bench to bedside successfully. This work reviews the ischemic cascade, agents targeting steps within the cascade, and potential reasons for lack of translation. Additional therapeutic targets are highlighted and areas requiring further investigation are discussed. It is clear that alternative targets need to be pursued, such as the role glia play in neurological injury and recovery, particularly the interactions between neurons, astrocytes, microglia, and the vasculature. Similarly, the biphasic nature of many signaling molecules such as matrix metalloproteinases and high-mobility group box 1 protein must be further investigated to elucidate periods of detrimental versus beneficial activity.