母体抗炎药对手术麻醉诱发的后代小鼠神经炎症和认知障碍的影响

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1481630
Dongdong Chai, Hong Jiang, Hua Liu
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引用次数: 0

摘要

背景:母体手术结合全身麻醉对神经炎症以及后代学习和记忆障碍发展的影响仍不清楚。本研究利用无病原体开腹手术模型来研究妊娠后三个月期间的这些变化及其对抗炎药物的反应:方法:对胚胎期为 14.5 天(E 14.5)的 C57BL/6 妊娠小鼠单独进行七氟醚麻醉或进行开腹手术。在出生后 7、14、21 和 28 天(P7、P14、P21 和 P28)对神经炎症反应进行评估。Tau磷酸化和认知能力分别在P28和P30时进行评估。随后评估了围手术期布洛芬(60 毫克/千克)对上述变化的影响:结果:在开腹手术组,后代小鼠大脑(包括大脑皮层和海马)中的炎症因子(IL-4、IL-8、IL-17A、TGF-β、M-CSF、CCL2)水平从 P7 到 P28 一直持续升高。在 P14 时,虽然大多数炎症细胞因子没有统计学差异,但在 P28 时,在额叶皮层和海马仍观察到炎症细胞因子的显著重新激活。此外,P28 和 P30 时还观察到 tau 磷酸化异常以及学习和记忆障碍。围手术期服用布洛芬可改善认知能力、减轻全身炎症反应并抑制额叶皮层和海马的tau异常磷酸化:我们的研究结果表明,认知功能障碍与炎症细胞因子和 tau 磷酸化水平的升高有关。开腹手术后的认知障碍和 tau 磷酸化至少会持续到 P28。研究表明,抗炎药物能迅速减轻大脑中的炎症反应,从而增强认知功能,同时还能影响神经系统的变化。这一发现可能会对制定旨在控制术后患者认知功能障碍的治疗策略产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The impact of maternal anti-inflammatory drugs on surgical anesthesia-induced neuroinflammation and cognitive impairment in offspring mice.

Background: The impact of maternal surgery combined with general anesthesia on neuroinflammation and the development of learning and memory impairment in offspring remains unclear. This study utilized a pathogen-free laparotomy model to investigate these changes during the second trimester, as well as their response to anti-inflammatory therapy.

Methods: C57BL/6 pregnant mice at the 14.5-day embryo stage (E 14.5) were either exposed to sevoflurane anesthesia alone or underwent laparotomy procedure. The neuroinflammatory response was evaluated at 7, 14, 21, and 28 days postnatal (P7, P14, P21, P28). Tau phosphorylation and cognitive ability were assessed at P28 and P30, respectively. The impact of perioperative administration of ibuprofen (60 mg/kg) on these aforementioned changes was subsequently evaluated.

Results: In the laparotomy group, levels of inflammatory factors (IL-4, IL-8, IL-17A, TGF-β, M-CSF, CCL2) in the brains of offspring mice, including the cerebral cortex and hippocampus, remained consistently elevated from P7 to P28. At P14, while the majority of inflammatory cytokine has no statistical difference, there was still a significant reactivation of inflammatory cytokines observed in the frontal cortex and hippocampus at P28. Furthermore, abnormal phosphorylation of tau and deficits in learning and memory were observed at P28 and P30. Administration of perioperative ibuprofen led to improvements in cognitive performance, reduction of systemic inflammation, and inhibiting abnormal phosphorylation of tau in the frontal cortex and hippocampus.

Conclusion: Our findings indicate that cognitive dysfunction is correlated with elevated levels of inflammatory cytokines and tau phosphorylation. Cognitive impairment and tau phosphorylation after laparotomy can persist at least until P28. Anti-inflammatory medications have been shown to enhance cognitive function by rapidly reducing inflammation in the brain, while also impacting neurological changes. This discovery may have implications for the development of treatment strategies aimed at managing cognitive impairment in post-operative patients.

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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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