Sevoflurane Alters Serum Metabolites in Elders and Aging Mice and Increases Inflammation in Hippocampus

J Inflamm Res. 2024 Feb 23:17:1241-1253. doi: 10.2147/JIR.S448959. eCollection 2024.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.

Keywords: RNA-seq; hippocampus; isatin; metabolomics; neuroinflammation; sevoflurane.

Grants and funding

This work was supported by funds from the National Natural Science Foundation of China (82104253 and 82300979), Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital (11300-412311-22043), Changning Maternity and Infant Health Hospital Scientific Research Staring Foundation (2020Y-15), and Shanghai Changning District Health Commission Youth Program (2022QN14).