Remote Limb Preconditioning Generates a Neuroprotective Effect by Modulating the Extrinsic Apoptotic Pathway and TRAIL-Receptors Expression

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• 作者：Wei Xu ; Wei Jin ; Xiaoxiao Zhang ; Jing Chen&#8230
• 关键词：Remote limb preconditioning ; Ischemic cerebral stoke ; Neuronal apoptosis ; TRAIL ; receptors
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：37
• 期：1
• 页码：169-182
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Neurosciences; Cell Biology; Neurobiology;
• 出版者：Springer US
• ISSN：1573-6830
• 卷排序：37

文摘

As remote limb preconditioning (RPC) ameliorates brain damage after ischemic cerebral stroke (ICS), the purpose of the present study was to explore the molecular mechanisms in the course of RPC. Results of TUNEL staining and cleaved caspase-3 expression showed that ischemia-induced neuronal apoptosis was inhibited by RPC. The expression changes in cleaved caspase-8, cFLIP, Bid itself, and its truncated form represented that RPC suppressed the activation of extrinsic apoptotic pathway during ICS. Then, the level of cytoplasmic cytochrome c was also decreased by RPC. In addition, RPC might partially suppress TNF-related apoptosis-inducing ligand (TRAIL)-induced extrinsic apoptosis through downregulation of TRAIL death receptors and upregulation of TRAIL decoy receptors. As a counterproof, immunoneutralization of TRAIL in dMCAO rats resulted in significant restraint of tissue damage and in a marked functional recovery. Our data complemented the knowledge of RPC neuroprotective mechanism and provided new evidence for its clinical application.