■术后认知功能障碍(POCD)是麻醉后发生的中枢神经系统并发症,尤其是老年人。然而,术后认知功能障碍的神经发病机制尚不清楚。本研究旨在通过代谢组学和转录组学分析评估七氟醚暴露对老年患者和衰老小鼠血清代谢产物和海马基因表达的影响,探讨七氟醚诱导POCD的发病机制。
■在七氟醚麻醉前和麻醉后1小时收集来自5名60岁以上患者的人血清样品。此外,12月龄小鼠(每组n=6)用七氟醚或假手术麻醉2小时.随后,收集血清和海马组织进行分析。使用BV2小胶质细胞进一步研究了Isatin与神经炎症之间的关系。
■七氟醚麻醉导致炎症通路激活,海马星形胶质细胞和小胶质细胞的增加,和神经炎症细胞因子的表达升高。比较分析确定了七氟醚麻醉后在人和小鼠血清中表现出变化的12种差异代谢物。值得注意的是,麻醉后,Isatin水平明显下降。值得注意的是,麻醉后显著降低,一种已知刺激小胶质细胞增殖和促炎基因表达的因子,小胶质细胞是炎症反应中的关键细胞类型。
■七氟醚在老年患者和衰老小鼠中诱导的血清代谢物改变,随后导致海马体炎症增加。
UNASSIGNED: Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD.
UNASSIGNED: Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between
isatin and neuroinflammation was conducted using BV2 microglial cells.
UNASSIGNED: Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably,
isatin levels were significantly decreased after anesthesia. Notably,
isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia-the pivotal cell type in inflammatory responses.
UNASSIGNED: Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.