Zhu Changlian, Wang Xiaoyang, Cheng Xiuyong, Qiu Lin, Xu Falin, Simbruner George, Blomgren Klas
Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, PR China.
Brain Res. 2004 Jan 16;996(1):67-75. doi: 10.1016/j.brainres.2003.10.013.
Hypothermia is possibly the single most effective method of neuroprotection developed to date. However, the mechanisms are not completely understood. The aim of this study was to investigate the effects of post-ischemic hypothermia on brain injury and apoptotic neuronal cell death as well as related biochemical changes after neonatal hypoxia-ischemia (HI). Seven-day-old rats were subjected to left common carotid artery ligation and hypoxia (7.8%) for 1 h. Systemic hypothermia was induced immediately after hypoxia-ischemia, and body temperature was maintained at 30 degrees C for 10 h. The normothermic group was kept at 36 degrees C. Brain infarct volumes and neuronal loss in the CA1 area of the hippocampus were significantly reduced at 72 h post-HI in the hypothermia group. Cytochrome c release and activation of caspase-3 and -2 at 24 h post-HI were significantly diminished by hypothermia. The numbers of cytochrome c- and TUNEL-positive cells in the cortex and dentate gyrus of the hippocampus were significantly reduced in the hypothermia group compared with the normothermia group at 72 h post-HI. These results indicate that hypothermia may, at least partially, act through inhibition of the intrinsic pathway of caspase activation in the neonatal brain, thereby preventing apoptotic cell death.
体温过低可能是迄今为止所开发的最有效的单一神经保护方法。然而，其机制尚未完全明确。本研究旨在探讨新生儿缺氧缺血（HI）后缺血性体温过低对脑损伤、凋亡性神经元细胞死亡以及相关生化变化的影响。将7日龄大鼠左侧颈总动脉结扎并给予缺氧（7.8%）处理1小时。缺氧缺血后立即诱导全身低温，体温维持在30℃达10小时。正常体温组维持在36℃。在HI后72小时，低温组海马CA1区的脑梗死体积和神经元损失显著减少。低温显著降低了HI后24小时细胞色素c的释放以及caspase-3和-2的激活。与正常体温组相比，HI后72小时低温组皮质和海马齿状回中细胞色素c和TUNEL阳性细胞的数量显著减少。这些结果表明，低温可能至少部分地通过抑制新生大脑中caspase激活的内源性途径起作用，从而防止凋亡性细胞死亡。
