Role of exosomes induced by remote ischemic preconditioning in neuroprotection against cerebral ischemia
Role of exosomes induced by remote ischemic preconditioning in neuroprotection against cerebral ischemia
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DOI：
10.1097/wnr.0000000000001280
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发表时间：
2019-08-14
期刊：
影响因子：
1.7
通讯作者：
Ji, Xunming
中科院分区：
文献类型：
--
作者：
Li, Yang;Ren, Changhong;Ji, Xunming
远程缺血预处理（RIPC）是缺血性中风神经保护的有效方案。外泌体是释放到血液中的细胞外囊泡，它们可以在全身传递信号。多项研究表明 RIPC 会导致循环外泌体发生许多变化。然而，RIPC 诱导的外泌体在神经保护中的作用仍有待确定。在当前的研究中，我们证明，与接受非 RIPC 处理小鼠的外泌体输注的对照组相比，输注 RIPC 处理小鼠的富集血浆外泌体可显着减轻脑缺血小鼠模型中的梗死面积。进一步的研究表明，输注 RIPC-外泌体可显着改善神经功能。与上述发现一致，我们发现接受 RIPC 的小鼠血浆外泌体中缺氧诱导转录因子 (HIF)-1 α 的水平显着高于对照组小鼠，这可能通过 HIF-1 α 诱导的信号（包括增强的缺氧耐受性）促进 RIPC 外泌体诱导的神经保护。据我们所知，这是首次证明 RIPC 通过诱导神经保护性外泌体来预防脑缺血。版权所有 (C) 2019 Wolters Kluwer Health, Inc. 保留所有权利。
Remote ischemic preconditioning (RIPC) is an effective regimen for neuroprotection in ischemic stroke. Exosomes are extracellular vesicles released into the blood, where they can transfer signals throughout the body. Several studies have demonstrated that RIPC leads to many changes in circulating exosomes. However, the role of RIPC-induced exosomes in neuroprotection remains to be determined. In the current study, we demonstrate that infusion of enriched plasma exosomes from RIPC-treated mice significantly attenuates infarction size in a murine model of cerebral ischemia compared to control group receiving infusion of exosomes from non-RIPC-treated mice. Further studies show that infusion of RIPC-exosomes markedly improves neurological functions. In line with the above findings, we find that the level of hypoxia inducible transcription factor (HIF)-1 alpha is significantly higher in plasma exosomes from mice subjected to RIPC than those from control mice, which could have contributed to the RIPC-exosome-induced neuroprotection through HIF-1 alpha-induced signals including the enhanced tolerance to hypoxia. To our knowledge, this is the first to demonstrate RIPC protects against cerebral ischemia through inducing neuroprotective exosomes. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.