Xenon preconditioning reduces brain damage from neonatal asphyxia in rats
Xenon preconditioning reduces brain damage from neonatal asphyxia in rats
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DOI：
10.1038/sj.jcbfm.9600184
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发表时间：
2006-02-01
影响因子：
6.3
通讯作者：
Maze, M
中科院分区：
文献类型：
--
作者：
Ma, DQ;Hossain, M;Maze, M
在体外和体内的缺氧-缺血损伤模型中，当在侮辱期间和之后给予氙气时，氙气可以减轻正在进行的神经元损伤。在目前的研究中，我们试图调查是否可以观察到在侮辱前给予氙气的神经保护效果，也就是所谓的“预适应”。在神经元-神经胶质细胞共培养中，氙预暴露2 h可使缺氧缺糖24 h的细胞乳酸脱氢酶释放呈浓度依赖性减少；蛋白质合成抑制剂放线菌酮可取消氙预处理的作用。氙气预处理减少缺氧缺糖海马片培养模型中碘化丙啶的染色。在7日龄大鼠缺氧-缺血损伤的新生儿窒息体内模型中，在损伤后7天进行评估时，氙气预适应可减少脑梗塞范围。此外，神经功能在损伤后30天也有明显改善。氙气暴露后，磷酸化cAMP(环磷酸腺苷3‘，5’-单磷酸)反应元件结合蛋白(PCREB)表达增加。此外，氙气还上调了存活蛋白Bcl2和脑源性神经营养因子的表达。这些研究为氙气的预适应效应提供了证据，这可能是由pCREB调节的蛋白质合成引起的，这些蛋白质促进了神经元损伤后的存活。
Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3',5'-monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.