氙改善小鼠长期认知功能、减少神经元缺失和慢性神经炎症并提高颅脑损伤后小鼠的存活率
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Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice
背景与目的
氙是一种惰性气体，具有神经保护功能，可改善年轻成年小鼠在受到可控性大脑皮质冲击后的短期和长期结局。本项后续研究旨在探讨氙对远期结局和生存的影响。
方 法
C57BL/6N年轻成年雄性小鼠(72只)接受单次可控性大脑皮质冲击或假手术，并用氙(75% Xe:25% O2)或对照气体(75% N2:25% O2)进行处理。结果测量:(1) 24小时病灶体积和神经学结局评分；（2）2周和20个月的情境恐惧条件反射；(3)量化胼胝体脑白质；(4)神经炎症和神经元缺失的免疫组织学评估；(5)长期生存率。
结 果
氙处理显著减少继发性损伤(P<0.05)，改善短期前庭运动功能(P<0.01)，预防晚期迟发性颅脑损伤(TBI)相关记忆障碍的发生。氙处理减少了20个月时的对侧胼胝体脑白质缺失以及对侧海马CA1和齿状回区域的神经元缺失。氙的长期神经保护作用与联想记忆相关的多个大脑区域的神经炎症显著减少有关(P<0.05)，包括减少反应性星形细胞胶质化和小胶质细胞增殖。损伤后12个月，与对照组相比，氙处理组存活率显著提高(P<0.05)。
结 论
TBI后氙处理可改善远期临床相关结局和生存率。我们的研究结果表明，TBI后不久进行氙处理，可能对治疗脑外伤患者有长期好处。
原始文献摘要
Campos-Pires R, Hirnet T, Valeo F, et al. Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice[J]. Br J Anaesth 2019 07;123(1). DOI:10.1016/j.bja.2019.02.032.
Background: Xenon is a noble gas with neuroprotective properties that can improve short and long-term outcomes in young adult mice after controlled cortical impact. This follow-up study investigates the effects of xenon on very long term outcomes and survival.
Methods: C57BL/6N young adult male mice (n=72) received single controlled cortical impact or sham surgery and were treated with either xenon (75% Xe:25% O2) or control gas (75% N2:25% O2). Outcomes measured were: (i) 24 h lesion volume and neurological outcome score; (ii) contextual fear conditioning at 2 weeks and 20 months; (iii) corpus callosum white matter quantification; (iv) immunohistological assessment of neuroinflammation and neuronal loss; and (v) long-term survival.
Results: Xenon treatment signifificantly reduced secondary injury (P<0.05), improved short-term vestibulomotor function (P<0.01), and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reduced white matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 and dentate gyrus areas at 20 months. Xenon’s long-term neuroprotective effects were associated with a signifificant (P<0.05) reduction in neuroinflflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved signifificantly (P<0.05) in xenontreated animals compared with untreated animals up to 12 months after injury.
Conclusions: Xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefifits in the treatment of brain trauma patients.
麻醉学文献进展分享
贵州医科大学高鸿教授课题组
翻译：冯玉蓉 编辑：何幼芹 审校：王贵龙