The effects of a solitary neonatal exposure to anesthesia plus surgery (anesthesia/surgery) on cognitive function and the underlying mechanism in developing brains remains largely undetermined. We, therefore, set out to investigate the impact of single exposure to anesthesia/surgery in neonatal mice. Six-day-old male and female mice received abdominal surgery under 3% sevoflurane plus 50% oxygen for 2 h. The new object recognition (NOR) and Morris water maze (MWM) were used to evaluate cognitive function in young adult mice. Western blot, ELISA and RT-PCR were used to measure levels of NR2B and IL-6 in medial prefrontal cortex and IL-6 in blood of the mice. We employed siRNA and IL-6 antibody in the interaction studies. The anesthesia/surgery decreased the ratio of novel time to novel plus familiar time in NOR and the number of platform crossings, but not escape latency, in MWM compared to sham condition. The mice in anesthesia/surgery group had increased NR2B expression in medial prefrontal cortex, and IL-6 amounts in blood and medial prefrontal cortex. Local injection of siRNA in medial prefrontal cortex alleviated the anesthesia/surgery-induced cognitive impairment. IL-6 antibody mitigated the anesthesia/surgery-induced upregulation of NR2B and cognitive impairment in young adult mice. These results suggest that a single neonatal exposure to anesthesia/surgery causes impairment of memory, but not learning, in young adult mice through IL-6-regulated increases in NR2B concentrations in medial prefrontal cortex, highlighting the need for further research on the underlying mechanisms of anesthesia/surgery's impact on cognitive function in developing brains.

中文翻译：

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新生小鼠单次接受麻醉/手术会导致年轻成年小鼠认知障碍

单独的新生儿接受麻醉加手术（麻醉/手术）对认知功能的影响以及大脑发育的潜在机制在很大程度上尚未确定。因此，我们着手研究单次麻醉/手术对新生小鼠的影响。六天大的雄性和雌性小鼠在 3% 七氟烷加 50% 氧气下接受腹部手术 2 小时。新的物体识别（NOR）和莫里斯水迷宫（MWM）被用来评估年轻成年小鼠的认知功能。采用Western blot、ELISA和RT-PCR检测小鼠内侧前额叶皮层NR2B、IL-6以及血液中IL-6的水平。我们在相互作用研究中使用了 siRNA 和 IL-6 抗体。与假手术条件相比，麻醉/手术降低了 NOR 中新时间与新加熟悉时间的比率，以及 MWM 中平台穿越的次数，但没有逃避潜伏期。麻醉/手术组小鼠内侧前额叶皮质中NR2B表达增加，血液和内侧前额叶皮质中IL-6含量增加。内侧前额皮质局部注射 siRNA 可减轻麻醉/手术引起的认知障碍。IL-6 抗体减轻了年轻成年小鼠麻醉/手术引起的 NR2B 上调和认知障碍。这些结果表明，单次新生儿暴露于麻醉/手术会通过 IL-6 调节内侧前额叶皮质中 NR2B 浓度的增加，导致年轻成年小鼠的记忆受损，但不会损害学习能力，这突出表明需要进一步研究其潜在机制麻醉/手术对大脑发育中认知功能的影响。