Gene Expression Variations Induced by Sevoflurane in Glia and Glioma Cells and the Role of EPHA3 in Sevoflurane's Anti-Glioma Effect.

Abstract

Introductions: Sevoflurane, a commonly used anesthetic in surgery, can produce anesthetic effects such as sedation and muscle relaxation upon inhalation, which may lead to postoperative cognitive dysfunction. However, the molecular mechanism by which sevoflurane affects nervous system diseases like glioma remains unclear.

Method: In this study, we analyzed high-throughput single-cell transcriptome data of sevoflurane treatment and identified immune cells that play crucial roles in biological processes such as the immunoinflammatory response and the maintenance of the blood- -brain barrier. A total of 11,244 genes and their variations were obtained by analyzing the cell development trajectory. Additionally, 10 key genes affected by sevoflurane were manually retrieved, and their protein-protein interaction network was constructed. The Chinese Glioma Genome Atlas (CGGA) dataset was utilized for survival analysis.

Results: This article reveals that sevoflurane can generate anesthetic effects through signaling pathways such as the immunoinflammatory response, neuronal differentiation, and the maintenance of the blood-brain barrier, all of which have implications for organ injury and protection. Meanwhile, genes that play a key role in these immune pathways, such as the DAAM2 and EPHA3 genes, are significantly associated with the survival of glioma patients. This association implies that sevoflurane's influence on these genes might potentially affect postoperative cognitive dysfunction and the overall outcome of organ-organ interactions during and after surgery. Moreover, the experimental results demonstrated that sevoflurane inhibits the invasion and migration of glioma cells by suppressing the expression of EPHA3.

Conclusion: The discovery of this new target may pave the way for identifying causative gene regulation events and emphasize personalized treatments for nervous system diseases.