Xenon preconditioning reduces brain damage from neonatal asphyxia in rats

被引:146
作者
Ma, DQ
Hossain, M
Pettet, GKJ
Luo, Y
Lim, T
Akimov, S
Sanders, RD
Franks, NP
Maze, M
机构
[1] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Anaesthet Intens Care & Pain Med, Fac Med, London SW10 9NH, England
[2] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Biophys Sect, London, England
关键词
hypoxia-ischaemia; neuroprotection; preconditioning; xenon;
D O I
10.1038/sj.jcbfm.9600184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:199 / 208
页数:10
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