Key Laboratory of Anesthesia and Organ Protection (Zunyi Medical University), Ministry of Education, Zunyi Medical University, Zunyi, China.
Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.
CNS Neurosci Ther. 2024 Aug;30(8):e14922. doi: 10.1111/cns.14922.
The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia.
First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed.
A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity.
In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.
全麻诱导的可逆性意识丧失的机制尚不清楚。最近的研究揭示了髓鞘和少突胶质细胞（OLs）在大脑高级功能中的关键作用。然而，髓鞘是否主动参与全麻的调节尚不清楚。本研究旨在探讨髓鞘在异氟醚麻醉诱导的意识改变调节中的作用及其可能的机制。
首先建立全脑和特定神经核的脱髓鞘模型，以研究髓鞘在全麻调节中的潜在作用及其可能的区域特异性。然后对脱髓鞘核进行 c-Fos 染色，以验证髓鞘缺失对神经元活性的影响。最后，通过光纤光度钙信号记录脱髓鞘小鼠在异氟醚麻醉期间神经元的活动。记录和分析相关行为指标和脑电图。
脱髓鞘小鼠异氟醚麻醉后的苏醒时间延长，提示髓鞘参与调节全麻。LPC 对特定核的脱髓鞘进一步阐明了髓鞘对异氟醚麻醉调节的区域特异性作用。脱髓鞘对特定核异氟醚麻醉的影响与神经元对异氟醚麻醉的影响一致。最后，我们发现髓鞘在调节异氟醚麻醉中的作用机制可能是通过调节神经元活性。
总之，不同神经核中的髓鞘在调节异氟醚麻醉过程中起着重要作用。髓鞘在调节异氟醚麻醉中的可能机制是全麻过程中髓鞘完整性通过调节神经元活性。我们的研究结果增强了对髓鞘功能的理解，为研究全麻的神经机制提供了新的视角。
