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首页> 外文期刊>The European Journal of Neuroscience >Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia-ischemia.
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Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia-ischemia.

机译:缺血内轻度低温可预防新生儿脑缺氧缺血后神经元细胞死亡和组织丢失。

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摘要

The effectiveness of hypothermia in preventing ischemic brain damage depends on when it is started. The purpose of this study was to investigate the effects of temperature reduction during a hypoxic-ischemic (HI) insult on brain injury and signalling pathways of neuronal cell death and survival. Seven-day-old mice were subjected to left common carotid artery ligation and hypoxia (10% oxygen) at different temperatures (37, 36 or 34 degrees C) for 50 min. Brain injury at 7 days post-HI was significantly reduced from 67.4% at 37 degrees C to 31.6% at 36 degrees C and 10% at 34 degrees C, with no observable injury in the cortex of the 34 degrees C group. Cytochrome c release, caspase-3 activation and apoptosis-inducing factor translocation from mitochondria to nuclei were all significantly inhibited after intraischemic temperature reduction. Concurrently, the cell survival signalling pathway involving Akt was significantly sustained (the phosphorylated form of Akt was maintained) when the hypoxia temperature was decreased. These results indicate that intraischemic hypothermia diminished apoptosis through inhibition of both caspase-dependent and caspase-independent neuronal cell death pathways and promoted cell survival by inhibition of phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing neuronal cell death.
机译:低温预防缺血性脑损伤的有效性取决于何时开始。这项研究的目的是调查在缺氧缺血(HI)损伤过程中温度降低对脑损伤以及神经元细胞死亡和存活的信号通路的影响。七日龄小鼠在不同温度(37、36或34摄氏度)下经受左颈总动脉结扎和缺氧(10%氧气)达50分钟。 HI后7天的脑损伤从37摄氏度的67.4%显着降低到36摄氏度的31.6%和34摄氏度的10%,在34摄氏度组的皮质中没有可观察到的损伤。缺血内温度降低后,细胞色素c的释放,caspase-3的激活和细胞凋亡诱导因子从线粒体向细胞核的转移均受到明显抑制。同时,当降低低氧温度时,涉及Akt的细胞存活信号通路得以显着维持(维持Akt的磷酸化形式)。这些结果表明,缺血内低温通过抑制caspase依赖性和caspase非依赖性神经元细胞死亡途径而减少了细胞凋亡,并且通过抑制新生脑中磷酸化的Akt去磷酸化来促进细胞存活,从而防止了神经元细胞死亡。

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