Zhu Changlian, Wang Xiaoyang, Xu Falin, Qiu Lin, Cheng Xiuyong, Simbruner George, Blomgren Klas
Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Eur J Neurosci. 2006 Jan;23(2):387-93. doi: 10.1111/j.1460-9568.2005.04581.x.
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.
低温预防缺血性脑损伤的有效性取决于其开始的时间。本研究的目的是探讨在缺氧缺血（HI）损伤期间降温对脑损伤以及神经元细胞死亡和存活信号通路的影响。对7日龄小鼠进行左侧颈总动脉结扎，并在不同温度（37、36或34摄氏度）下缺氧（10%氧气）50分钟。HI后7天的脑损伤从37摄氏度时的67.4%显著降低至36摄氏度时的31.6%以及34摄氏度时的10%，在34摄氏度组的皮质中未观察到损伤。缺血期间降温后，细胞色素c释放、半胱天冬酶-3激活以及凋亡诱导因子从线粒体向细胞核的转位均受到显著抑制。同时，当缺氧温度降低时，涉及Akt的细胞存活信号通路显著维持（Akt的磷酸化形式得以保持）。这些结果表明，缺血期间低温通过抑制半胱天冬酶依赖性和非依赖性神经元细胞死亡途径减少凋亡，并通过抑制新生脑内磷酸化Akt的去磷酸化促进细胞存活，从而预防神经元细胞死亡。
