Zhang Linyong, Ke Zhidan, Zhang Ning, Wang Dechuan, Zhou Liang
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
Key Laboratory of Anesthesia and Organ Protection (Zunyi Medical University), Ministry of Education, Zunyi Medical University, Zunyi, 563003, China.
Sci Rep. 2025 Jan 9;15(1):1546. doi: 10.1038/s41598-025-85834-1.
As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change. Furthermore, disrupted proliferation of oligodendrocyte precursor cells (OPCs) contributes to repeated sevoflurane exposure-induced myelin defect. This may be owing to an accumulated tuberous sclerosis complex 1 (TSC1) expression and inhibition of mammalian target of rapamycin (mTOR) signaling, leading to the unbalance of TSC1-mTORC1 activity after repeated sevoflurane exposure, which is critical for proper myelination of the central nervous system (CNS). Moreover, repeated sevoflurane exposure aggregates myelination defect in the cuprizone-induced demyelination model. Together, our present work establishes the role of sevoflurane exposure in myelin integrity in the PFC of the adult male mice and provides a new insight to elucidate the mechanism of GAs-induced brain dysfunctions.
作为手术中最常用的全身麻醉剂（GA）之一，大量研究已证明七氟醚暴露对发育中的大脑和老年大脑的髓鞘形成有有害影响。然而，七氟醚暴露对成年大脑中完整髓鞘结构的影响却鲜有发现。在此，我们表明，成年雄性小鼠前额叶皮质（PFC）中，反复暴露于七氟醚而非单次暴露，会导致髓鞘形成减少和髓鞘超微结构异常，而前额叶皮质被认为是全身麻醉介导意识改变的关键脑区。此外，少突胶质前体细胞（OPC）增殖的破坏导致了反复七氟醚暴露诱导的髓鞘缺陷。这可能是由于结节性硬化复合物1（TSC1）表达的积累以及对雷帕霉素哺乳动物靶点（mTOR）信号通路的抑制，导致反复七氟醚暴露后TSC1 - mTORC1活性失衡，而这对中枢神经系统（CNS）的正常髓鞘形成至关重要。此外，在铜螯合剂诱导的脱髓鞘模型中，反复七氟醚暴露会加剧髓鞘形成缺陷。总之，我们目前的工作确立了七氟醚暴露在成年雄性小鼠前额叶皮质髓鞘完整性中的作用，并为阐明全身麻醉剂诱导脑功能障碍的机制提供了新的见解。
