Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia
Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia
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DOI：
10.1161/01.str.0000198867.31134.ac
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发表时间：
2006-02-01
期刊：
影响因子：
8.3
通讯作者：
Thoresen, M
中科院分区：
文献类型：
--
作者：
Dingley, J;Tooley, J;Thoresen, M
背景和目的-缺氧缺血性损伤后的脑损伤通过凋亡/坏死级联发展。谷氨酸过度释放和n -甲基- d -天冬氨酸（NMDA）受体过度激活（兴奋性毒性）被认为触发了这一过程。氙是一种无毒的麻醉气体，可减少神经递质释放，并在功能上拮抗NMDA受体。如果分娩后神经毒性过程继续发展，对缺氧缺血性新生儿给予氙气可能在临床上有效。我们试图确定在初始缺氧缺血性损伤后给予氙气是否具有神经保护作用。方法：50只7日龄大鼠单侧颈动脉结扎术后90分钟缺氧损伤。然后，他们随机呼吸两种气体混合物中的一种，持续3小时：50% Xe/30% o /20% N-2或30% o /70% N-2。结果：缺氧缺血存活一周后，氙气组出现明显的全局保护（损伤减少80%）；皮层/白质（88%对25%）、海马（62%对0%）、基底神经节（81%对25%）和丘脑（50%对0%；非氙气组和氙气组的整体损伤评分百分比分别为）。结论：新生大鼠缺氧缺血后给予3小时氙气可提供短期神经保护。这一发现表明围产期窒息后氙气治疗也具有神经保护作用。由于氙气不会引起其他神经毒性作用，并且在广泛的麻醉研究中显示出最小的副作用，因此它将成为人类围产期缺氧缺血后治疗的理想候选药物。
Background and Purpose - Brain injury after hypoxic-ischemic insults evolves via an apoptotic/necrotic cascade. Glutamate over release and N-methyl-D-aspartate (NMDA) receptor over activation (excitotoxicity) are believed to trigger this process. Xenon is a nontoxic anesthetic gas that reduces neurotransmitter release and functionally antagonizes NMDA receptors. Administering xenon to hypoxic-ischemic newborns might be clinically effective if the neurotoxic processes continue evolving after delivery. We sought to determine whether xenon administration after the initial hypoxic-ischemic insult was neuroprotective.Methods - Fifty 7-day-old rats received a 90-minute hypoxic insult after unilateral carotid ligation. They were then randomized to breathe 1 of 2 gas mixtures for 3 hours: 50% Xe/30% O-2/20% N-2 or 30% O-2/70% N-2.Results - One week after hypoxic-ischemic survival, significant global protection was seen in the xenon group (80% less injury); cortex/white matter (88% versus 25%), hippocampus (62% versus 0%), basal ganglia (81% versus 25%), and thalamus (50% versus 0%; percentage of global damage score in nonxenon versus xenon groups, respectively).Conclusions - Three hours of xenon administration commenced after hypoxia-ischemia in neonatal rats provides short-term neuroprotection. This finding suggests that treatment with xenon after perinatal asphyxia would also be neuroprotective. Because xenon does not cause other neurotoxic effects and has demonstrated minimal side effects in extensive anesthesia studies, it would make an ideal candidate for the treatment after human perinatal hypoxia-ischemia.