Neuroprotection against Traumatic Brain Injury by Xenon, but Not Argon, Is Mediated by Inhibition at the N-Methyl-D-Aspartate Receptor Glycine Site
Neuroprotection against Traumatic Brain Injury by Xenon, but Not Argon, Is Mediated by Inhibition at the N-Methyl-D-Aspartate Receptor Glycine Site
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DOI：
10.1097/aln.0b013e3182a2a265
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发表时间：
2013-11-01
期刊：
影响因子：
8.8
通讯作者：
Dickinson, Robert
中科院分区：
文献类型：
--
作者：
Harris, Katie;Armstrong, Scott P.;Dickinson, Robert
背景：氙是一种惰性麻醉气体，在脑损伤模型中具有神经保护作用。作者研究了惰性气体（如氙、氩、氪、氖和氦）在创伤性脑损伤体外模型中的神经保护机制。方法：作者使用小鼠器官型海马脑切片进行体外模型，遭受局灶性机械创伤，通过碘化丙啶荧光定量损伤。膜片钳电生理学用于研究惰性气体对 N-甲基-d-天冬氨酸受体和 TREK-1 通道的影响，这两个分子靶点可能在神经保护中发挥作用。结果：损伤后应用时，氙气 (50%) 和较小程度的氩气 (50%) 对创伤性损伤具有神经保护作用（损伤后 72 小时，氙气的保护率为 431% [N = 104]；氩气30 +/- 6% 保护 [N = 44]；平均值 +/- SEM)。氦、氖和氪缺乏神经保护作用。氙 (50%) 可在创伤后 48 小时内防止继发性损伤的发生。氩气 (50%) 可减轻继发性损伤，但效果不如氙气（损伤后 72 小时，氙气可减少继发性损伤 50 +/- 5% [N = 104]；氩气可减少 34 +/- 8% [N = 44]；平均值 +/- SEM）。甘氨酸可逆转氙的神经保护作用，但不能逆转氩的神经保护作用，这与 N-甲基-d-天冬氨酸受体甘氨酸位点的竞争性抑制一致，介导氙对创伤性脑损伤的神经保护作用。氙会抑制 N-甲基-d-天冬氨酸受体并激活 TREK-1 通道，而氩、氪、氖和氦对这些离子通道没有影响。结论：氙对创伤性脑损伤的神经保护作用可以通过增加甘氨酸浓度来逆转，这与抑制 N-甲基-d-天冬氨酸受体甘氨酸位点在氙神经保护中发挥重要作用一致。氩气和氙气的作用机制不同。
Background: Xenon, the inert anesthetic gas, is neuroprotective in models of brain injury. The authors investigate the neuroprotective mechanisms of the inert gases such as xenon, argon, krypton, neon, and helium in an in vitro model of traumatic brain injury.Methods: The authors use an in vitro model using mouse organotypic hippocampal brain slices, subjected to a focal mechanical trauma, with injury quantified by propidium iodide fluorescence. Patch clamp electrophysiology is used to investigate the effect of the inert gases on N-methyl-d-aspartate receptors and TREK-1 channels, two molecular targets likely to play a role in neuroprotection.Results: Xenon (50%) and, to a lesser extent, argon (50%) are neuroprotective against traumatic injury when applied after injury (xenon 431% protection at 72h after injury [N = 104]; argon 30 +/- 6% protection [N = 44]; mean +/- SEM). Helium, neon, and krypton are devoid of neuroprotective effect. Xenon (50%) prevents development of secondary injury up to 48h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon (xenon 50 +/- 5% reduction in secondary injury at 72h after injury [N = 104]; argon 34 +/- 8% reduction [N = 44]; mean +/- SEM). Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive inhibition at the N-methyl-d-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-d-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels.Conclusions: Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-d-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.