Clinical application of preconditioning and postconditioning to achieve neuroprotection.
Clinical application of preconditioning and postconditioning to achieve neuroprotection.
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DOI：
10.1007/s12975-012-0224-3
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发表时间：
2013-02
影响因子：
6.9
通讯作者：
Gonzalez, Nestor R.
中科院分区：
文献类型：
--
作者：
Dezfulian, Cameron;Garrett, Matthew;Gonzalez, Nestor R.
缺血预处理是一种由组织中短暂的亚临界缺血诱导的内源性保护形式。对缺血具有高敏感性的器官，如心脏、脑和脊髓代表了缺血调节的潜在治疗应用的最关键和潜在有希望的靶点。许多临床前研究已经系统地研究了预处理和后处理的分子途径和潜在益处，并取得了可喜的结果。本文综述了脑预处理和脑后处理的研究进展，并重点介绍了这些神经保护形式的临床应用。对术语预处理和后处理进行了系统的Medline检索。选择并分析了与神经系统和人类应用相关的出版物。预处理和后处理似乎提供了相似的神经保护水平。预处理窗口的好处，可以细分为早期和晚期的影响，这取决于是否出现后立即亚致死应力或延迟天的效果。一般而言，早期效应与关键蛋白（膜受体、线粒体呼吸链）的翻译后修饰相关，而晚期效应是基因上调或下调的结果。短暂性脑缺血发作似乎代表了一种临床相关的预处理形式，通过诱导脑缺血耐受和降低后续卒中的严重程度。远程形式的缺血预处理和缺血后处理在临床研究中更常用，因为远程应用降低了损伤所寻求保护的靶组织的风险。肢体短暂性缺血是诱导远程调节的首选方法，有证据支持其安全性。在各种中枢神经损伤风险人群中的临床研究，包括颈动脉疾病、颈脊髓病和蛛网膜下腔出血，显示损伤的替代标志物有所改善。有前途的临床前和早期临床研究指出，使用远程预处理和后处理治疗后，中枢神经损伤的替代标志物的改善，需要后续的系统研究，以解决有效性。应该通过仔细、精心设计的转化研究来克服将这些技术应用于紧迫的临床脑血管疾病所面临的挑战。
Ischemic conditioning is a form of endogenous protection induced by transient, subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such as the heart, the brain, and spinal cord represent the most critical and potentially promising targets for potential therapeutic applications of ischemic conditioning. Numerous preclinical investigations have systematically studied the molecular pathways and potential benefits of both pre- and post-conditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre-and post-conditioning, with an emphasis in the clinical application of these forms of neuroprotection. A systematic Medline search for the terms preconditioning and postconditioning was performed. Publications related to the nervous system and to human applications were selected and analyzed. Pre-and post-conditioning appear to provide similar levels of neuroprotection. The preconditioning window of benefit can be subdivided into early and late effects, depending on whether the effect appears immediately after the sublethal stress or with a delay of days. In general early effects have been associated post-translational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up-or down-regulation. Transient ischemic attacks appear to represent a form of clinically relevant preconditioning by inducing ischemic tolerance in the brain and reducing the severity of subsequent strokes. Remote forms of ischemic pre- and post-conditioning have been more commonly used in clinical studies, as the remote application reduces the risk of injuring the target tissue for which protection is pursued. Limb transient ischemia is the preferred method of induction of remote conditioning with evidence supporting its safety. Clinical studies in a variety of populations at risk of central nervous damage including carotid disease, cervical myelopathy and subarachnoid hemorrhage have shown improvement in surrogate markers of injury. Promising preclinical and early clinical studies noting improvement in surrogate markers of central nervous injury after the use of remote pre- and post-conditioning treatments demand follow-up systematic investigations to address effectiveness. Challenges in the application of these techniques to pressing clinical cerebrovascular disease ought to be overcome through careful, well-designed, translational investigations.
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DOI：
10.1186/2040-7378-2-2
发表时间：
2010-01-21
期刊：
Experimental & translational stroke medicine
影响因子：
--
作者：
Durukan A;Tatlisumak T
通讯作者：
Tatlisumak T
影响因子：
37.8
作者：
Hoole, Stephen P.;Heck, Patrick M.;Dutka, David P.
通讯作者：
Dutka, David P.
影响因子：
4
作者：
Burda, Jozef;Danielisova, Viera;Burda, Rastislav
通讯作者：
Burda, Rastislav
瑞舒伐他汀预处理通过调节一氧化氮合酶表达对大鼠脊髓缺血提供神经保护
影响因子：
2.9
作者：
Die, Jun;Wang, Kunzheng;Shi, Zhibing
通讯作者：
Shi, Zhibing
影响因子：
2.1
作者：
He, Z;Crook, JE;McKinney, M
通讯作者：
McKinney, M