氙气对神经元损伤的体外和体内模型的影响。

Effects of xenon on in vitro and in vivo models of neuronal injury.

作者信息

Wilhelm Stefan, Ma Daqing, Maze Mervyn, Franks Nicholas P

机构信息

Chelsea & Westminster Hospital, London, United Kingdom.

出版信息

Anesthesiology. 2002 Jun;96(6):1485-91. doi: 10.1097/00000542-200206000-00031.

DOI:10.1097/00000542-200206000-00031

PMID:12170064

Abstract

BACKGROUND

Xenon, the "inert" gaseous anesthetic, is an antagonist at the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Because of the pivotal role that NMDA receptors play in neuronal injury, the authors investigated the efficacy of xenon as a neuroprotectant in both in vitro and in vivo paradigms.

METHODS

In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, glutamate, or oxygen deprivation and assessed by the release of lactate dehydrogenase into the culture medium. Increasing concentrations of either xenon or nitrogen (10-75% of an atmosphere) were coadministered and maintained until injury was assessed. In separate in vivo experiments, rats were administered N-methyl-dl-aspartate and killed 3 h later. Injury was quantified by histologic assessment of neuronal degeneration in the arcuate nucleus of the hypothalamus.

RESULTS

Xenon exerted a concentration-dependent protection against neuronal injury provoked by NMDA (IC(50) = 19 +/- 6% atm), glutamate (IC(50) = 28 +/- 8% atm), and oxygen deprivation (IC(50) = 10 +/- 4% atm). Xenon (60% atm) reduced lactate dehydrogenase release to baseline concentrations with oxygen deprivation, whereas xenon (75% atm) reduced lactate dehydrogenase release by 80% with either NMDA- or glutamate-induced injury. In an in vivo brain injury model in rats, xenon exerted a concentration-dependent protective effect (IC(50) = 78 +/- 8% atm) and reduced the injury by 45% at the highest xenon concentration tested (75% atm).

CONCLUSIONS

Xenon, when coadministered with the injurious agent, exerts a concentration-dependent neuroprotective effect at concentrations below which anesthesia is produced in rodents. Unlike either nitrous oxide or ketamine (other anesthetics with NMDA antagonist properties), xenon is devoid of both neurotoxicity and clinically significant adverse hemodynamic properties. Studies are proposed to determine whether xenon can be used as a neuroprotectant in certain clinical settings.

摘要

背景

氙气，这种“惰性”气态麻醉剂，是N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体的拮抗剂。由于NMDA受体在神经元损伤中起关键作用，作者在体外和体内模型中研究了氙气作为神经保护剂的功效。

方法

在小鼠神经元-神经胶质细胞共培养物中，通过NMDA、谷氨酸或缺氧引发损伤，并通过测定培养基中乳酸脱氢酶的释放来评估。同时给予递增浓度的氙气或氮气（大气浓度的10%-75%）并维持，直至评估损伤情况。在单独的体内实验中，给大鼠注射N-甲基-DL-天冬氨酸，3小时后处死。通过对下丘脑弓状核神经元变性的组织学评估来量化损伤。

结果

氙气对由NMDA（半数抑制浓度[IC50]=19±6%大气浓度）、谷氨酸（IC50=28±8%大气浓度）和缺氧（IC50=10±4%大气浓度）引发的神经元损伤具有浓度依赖性保护作用。在缺氧情况下，60%大气浓度氙气可将乳酸脱氢酶释放量降至基线浓度；而在NMDA或谷氨酸诱导的损伤中，75%大气浓度氙气可使乳酸脱氢酶释放量降低80%。在大鼠体内脑损伤模型中，氙气具有浓度依赖性保护作用（IC50=78±8%大气浓度），在测试的最高氙气浓度（75%大气浓度）下，损伤减少了45%。