Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

中文翻译：

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小鼠怀孕期间的七氟醚麻醉会引起铁缺乏症和抑制髓鞘生成，从而在后代引起认知障碍。

孕期孕妇接触麻醉剂会增加后代认知障碍的风险。脑铁代谢的平衡对于脑组织的发育至关重要。铁缺乏会影响髓鞘生成和神经组织发育，尤其是胎儿或婴儿，这在认知功能中起关键作用。我们旨在调查母体七氟醚（Sev）暴露是否通过诱导铁缺乏和抑制髓鞘生成而引起后代认知障碍。妊娠小鼠（妊娠第14天）用2％的Sev处理6小时。后代小鼠的认知功能由莫里斯水迷宫和情境恐惧条件试验确定。铁水平通过Perl的铁染色和同步加速器成像进行测定。收集后代小鼠（出生后第35天）的海马和皮质组织或脑微血管内皮细胞，并进行Western印迹和/或免疫组织化学以评估铁蛋白，转铁蛋白受体1（TfR1），铁转运蛋白-1（FpN1），髓磷脂碱性蛋白（ MBP），紧密连接蛋白ZO-1，occludin和claudin-5的水平。从出生后第30天开始，对后代进行铁疗法治疗30天，并测试上述指标。我们的结果表明，Sev大大降低了后代小鼠的大脑铁含量，损害了其认知功能。Sev降低了后代小鼠海马和皮质或大脑微血管内皮细胞中重链铁蛋白（FtH），轻链铁蛋白（FtL），MBP，ZO-1，occludin，claudin-5和FpN1的表达，并增加了TfR1，表明Sev引起了铁缺乏症并损害了后代大脑的髓鞘生成。有趣的是，铁疗法在出生后60天促进了髓鞘形成并改善了认知功能。我们的研究揭示了一种新的机制，该机制表明由Sev和髓磷脂形成障碍引起的铁缺乏症可能是脑铁减少的重要原因，可能是认知障碍的重要危险因素。在后代。有必要为后代提供铁补充剂，其母亲在怀孕期间会接触七氟醚。我们的研究发现了一种新的机制，该机制表明由Sev和髓磷脂形成障碍引起的铁缺乏症可能是由脑铁减少引起的，可能是后代认知障碍的重要危险因素。有必要为后代提供铁补充剂，其母亲在怀孕期间会接触七氟醚。我们的研究发现了一种新的机制，该机制表明由Sev和髓磷脂形成障碍引起的铁缺乏症可能是由脑铁减少引起的，可能是后代认知障碍的重要危险因素。有必要为后代提供铁补充剂，其母亲在怀孕期间会接触七氟醚。