Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment.
Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment.
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DOI：
10.1097/aln.0b013e3182834d77
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发表时间：
2013-03
期刊：
影响因子：
8.8
通讯作者：
Xie Z
中科院分区：
文献类型：
--
作者：
Shen X;Dong Y;Xu Z;Wang H;Miao C;Soriano SG;Sun D;Baxter MG;Zhang Y;Xie Z
最近的人口研究表明，儿童在早期多次暴露于麻醉和手术，认知障碍的风险增加。因此，我们建立了一个动物模型，多次与单次暴露的麻醉剂（S）在年轻与成年小鼠，旨在区分不同的麻醉在认知障碍中的作用。将6日龄和60日龄小鼠暴露于各种麻醉方案。然后，我们确定了麻醉对学习和记忆功能的影响，脑组织中促炎细胞因子白细胞介素-6和肿瘤坏死因子-α的水平，以及海马中小胶质细胞活化的标志物离子钙结合适配器分子1阳性细胞的数量。在这里，我们表明，每天两小时连续三天用3%七氟烷麻醉诱导认知障碍和神经炎症[例如，白细胞介素-6水平升高：151% ± 2.3（平均值± SD）vs 100% ± 9.0，P = 0.035，n = 6]。3%七氟烷每天两小时持续一天和9%地氟烷每天两小时持续三天的麻醉既未诱导认知障碍也未诱导神经炎症。最后，丰富的环境和抗炎治疗（酮咯酸）改善了七氟烷麻醉诱导的认知障碍。麻醉诱导的认知障碍可能取决于发育阶段、麻醉剂和暴露次数。这些研究结果还表明了麻醉诱导的认知障碍的细胞基础和潜在的预防和治疗策略，这可能最终导致更安全的麻醉护理和更好的儿童术后结局。
Recent population studies have suggested that children with multiple exposures to anesthesia and surgery at an early age are at an increased risk of cognitive impairment. We therefore have established an animal model with multiple versus single exposures of anesthetic(s) in young versus adult mice, aiming to distinguish the role of different anesthesia in cognitive impairment. Six day and 60 day-old mice were exposed to various anesthesia regimen. We then determined the effects of the anesthesia on learning and memory function, levels of pro-inflammatory cytokine interleukin-6 and tumor necrosis factor-α in brain tissues, and the amount of ionized calcium binding adaptor molecule 1 positive cells, the marker of microglia activation, in the hippocampus. Here we show that anesthesia with 3% sevoflurane two hours daily for three days induced cognitive impairment and neuroinflammation [e.g., increased interleukin-6 levels: 151% ± 2.3 (mean ± SD) versus 100% ± 9.0, P = 0.035, n = 6] in young, but not adult, mice. Anesthesia with 3% sevoflurane two hours daily for one day and 9% desflurane two hours daily for three days induced neither cognitive impairment nor neuroinflammation. Finally, an enriched environment and anti-inflammation treatment (ketorolac) ameliorated the sevoflurane anesthesia-induced cognitive impairment. Anesthesia-induced cognitive impairment may depend on developmental stage, anesthetic agent, and the number of exposures. These findings also suggest the cellular basis and the potential prevention and treatment strategies for the anesthesia-induced cognitive impairment, which may ultimately lead to safer anesthesia care and better postoperative outcomes for children.