Prolonged hypothermia exposure diminishes neuroprotection for severe ischemic-hypoxic primary neurons
Prolonged hypothermia exposure diminishes neuroprotection for severe ischemic-hypoxic primary neurons
复制标题
长时间的低温暴露会降低严重缺血缺氧原代神经元的神经保护作用
DOI：
10.1016/j.cryobiol.2016.01.003
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发表时间：
2016-04-01
期刊：
影响因子：
2.7
通讯作者：
Pan, Su-Yue
中科院分区：
文献类型：
--
作者：
Gao, Xiao-Ya;Zhu, Shu-Zhen;Pan, Su-Yue
本研究旨在找出对经历严重缺血和缺氧的神经细胞提供最佳保护的最佳亚低温(MH)条件。我们还试图确定更长时间的亚低温暴露是否会对这些细胞中的严重缺血和缺氧提供更好的保护。我们设计了一个原代神经元细胞模型，用于模拟严重中风、创伤或缺氧缺血性脑病患者的缺氧缺血状态。我们在OGD/R和不同的MH条件下，包括不同的温度和OGD/R暴露的时间，评估了这些神经元的活性。我们进一步探讨了最佳的MH条件对与线粒体凋亡途径相关的几个部分的影响：细胞内钙、活性氧自由基(ROS)和线粒体跨膜电位(MTP)。本研究结果表明，缺氧/复氧后细胞的凋亡率和细胞存活率明显不同(p<；0.001)。此外，我们的研究结果表明，长时间的MH降低了对AP和CVP的神经保护作用。我们还确定了最优的MH条件(34℃，4.5h)减少了细胞内钙，ROS，并恢复了MTP。这些结果表明，对于严重缺氧缺血的神经元，存在一种最佳的MH治疗策略，持续时间的延长可能会削弱神经保护，MH治疗可能通过抑制线粒体凋亡途径来启动神经保护。(C)2016年提交人。由Elsevier Inc.出版。这是一篇CC BY-NC-ND许可下的开放获取文章。
This study aimed to identify optimal mild hypothermic (MH) condition that would provide the best protection for neuronal cells undergoing severe ischemia and hypoxia. We also sought to determine if longer exposure to mild hypothermia would confer greater protection to severe ischemia and hypoxia in these cells. We designed a primary neuronal cell model for severe glucose and oxygen deprivation/reoxygenation (OGD/R) to simulate the hypoxic-ischemic condition of patients with severe stroke, trauma, or hypoxic-ischemic encephalopathy. We evaluated the viability of these neurons following 3 h of OGD/R and variable MH conditions including different temperatures and durations of OGD/R exposure. We further explored the effects of the optimal MH condition on several parts which are associated with mitochondrial apoptosis pathway: intracellular calcium, reactive oxygen species (ROS), and mitochondria] transmembrane potential (MTP). The results of this study showed that the apoptosis proportion (AP) and cell viability proportion (CVP) after OGD/R significantly varied depending on which MH condition cells were exposed to (p < 0.001). Further, our findings showed that prolonged MH reduced the neuroprotection to AP and CVP. We also determined that the optimal MH conditions (34 degrees C for 4.5 h) reduced intracellular calcium, ROS, and recovered MTP. These findings indicate that there is an optimal MH treatment strategy for severely hypoxia-ischemic neurons, prolonged duration might diminish the neuroprotection, and that MH treatment likely initiates neuroprotection by inhibiting the mitochondrial apoptosis pathway. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.