Reduction of ischemic brain damage by nitrous oxide and xenon
Reduction of ischemic brain damage by nitrous oxide and xenon
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DOI：
10.1097/01.wcb.0000087342.31689.18
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发表时间：
2003-10-01
影响因子：
6.3
通讯作者：
Abraini, JH
中科院分区：
文献类型：
--
作者：
David, HN;Leveille, F;Abraini, JH
缺血引起的脑损伤后的神经元死亡很大程度上取决于 N-甲基-D-天冬氨酸 (NMDA) 兴奋性谷氨酸受体的激活，该受体是许多假定的神经保护剂的靶标。虽然 NMDA 受体介导缺血性脑损伤，但阻断它们对人类来说是有害的。在此，作者研究了一氧化二氮或氙气这两种具有非常安全的临床特征的气态麻醉剂，最近被证明是 NMDA 受体的有效抑制剂，是否可以减少以下症状：（1）在大脑中动脉（MCAO）闭塞后给予体内缺血引起的脑损伤，这是使这些潜在的神经保护剂具有治疗价值所需的条件； (2) NMDA 诱导皮质细胞培养物中 Ca2+ 流入，这是兴奋性毒性神经元死亡中涉及的一个主要关键事件。作者表明，75 vol% 的一氧化二氮和 50 vol% 的氙气均可将皮质中的缺血性神经元死亡减少 70%，并进一步将 NMDA 诱导的 Ca2+ 流入减少 30%。此外，50% 的氙气（而不是 75% 体积的一氧化二氮）可以进一步减少纹状体（一种已知对神经保护干预具有抵抗力的皮层下结构）的缺血性脑损伤。然而，在较高浓度（75 vol%）下，氙表现出潜在的神经毒性作用。讨论了一氧化二氮和氙的神经保护作用和潜在神经毒性作用的机制，以及对人类可能的治疗意义。
Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death. The authors have shown that both nitrous oxide at 75 vol% and xenon at 50 vol% reduce ischemic neuronal death in the cortex by 70% and further decrease NMDA-induced Ca2+ influx by 30%. In addition, xenon at 50%, but not nitrous oxide at 75 vol%, further decreases ischemic brain damage in the striatum (a subcortical structure that is known to be resistant to neuroprotective interventions). However, at a higher concentration (75 vol%), xenon exhibits potentially neurotoxic effects. The mechanisms of the neuroprotective and potentially neurotoxic effects of nitrous oxide and xenon, as well as the possible therapeutic implications in humans, are discussed.