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Clinical Application of Preconditioning and Postconditioning to Achieve Neuroprotection

机译：预处理和后处理实现神经保护的临床应用

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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 postconditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre- and postconditioning, 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 postconditioning 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 posttranslational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up- or downregulation. 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 postconditioning 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 postconditioning 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.
机译：缺血性调节是组织中短暂，亚临界缺血引起的内源性保护形式。对缺血高度敏感的器官，例如心脏，大脑和脊髓，代表了缺血性调理的潜在治疗应用中最关键和最有希望的靶标。许多临床前研究已经系统地研究了预处理前后的分子途径和潜在益处，并取得了可喜的结果。这篇综述的目的是总结关于脑预处理和后处理的当前知识，重点是这些形式的神经保护的临床应用。进行了系统的MEDLINE搜索条件预处理和后处理。选择和分析了与神经系统和人类应用有关的出版物。预处理和后处理似乎提供类似水平的神经保护。受益的预处理窗口可以分为早期效应和晚期效应，具体取决于效应是在亚致死压力后立即出现还是延迟几天出现。通常，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，而晚期效应则是基因上调或下调的结果。短暂性脑缺血发作似乎通过诱导脑部缺血耐受并降低后续中风的严重性来代表一种临床上相关的预处理。远程形式的缺血预处理和后处理已在临床研究中更普遍地使用，因为远程应用可降低伤害对其进行保护的目标组织的风险。肢体短暂性缺血是诱导远程调节的首选方法，证据支持其安全性。在各种有中枢神经损伤风险的人群中进行的临床研究包括颈动脉疾病，宫颈脊髓病和蛛网膜下腔出血已显示出替代损伤标志物的改善。有远见的临床前和早期临床研究指出，在使用远程前后条件治疗后中枢神经损伤的替代指标有所改善，因此需要进行后续的系统研究以解决其有效性。应通过仔细，精心设计的翻译研究来克服将这些技术应用于治疗临床脑血管疾病的挑战。

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