Although it may come as a surprise to the millions of people who undergo general anesthesia each year for medical procedures, the biological mechanism of how different anesthetics block consciousness is still not fully understood. However, researchers may be one step closer after revealing how small immune cells in the brain called microglia are affected by general anaesthesia.
The research was presented in a paper published in eLife on 22/Dec/2023.
We found that microglia play an important role in regulating the body’s response to general anesthesia. Microglia are important cells of the immune system in the central nervous system (CNS) that play critical roles in CNS function and dysfunction.”
Bo Peng, Professor, Institute of Translational Brain Research, Fudan University, Shanghai, China
Previous research on microglia has shown that the cells’ behavior changes while under anesthesia, but this study is the first to show how microglia regulate neuronal activity in a brain region-specific way and play a key role in how it works. anesthesia.
The first glimpse of how microglia affect the effectiveness of anesthesia was inadvertently observed during another study and then confirmed through additional tests. Microglial depletion was induced in mice by inhibiting colony-stimulating factor receptor 1 (CSF1R) signaling. When microglia were killed with a CSF1R inhibitor called PLX5622, there was strong resistance to anesthesia. This resistance to anesthesia was observed with four different types of anesthesia with two different receptors and the observations were confirmed through electroencephalography (EEG) and electromyography (EMG) measurements.
Microglia also modulate network brain activity in a region-specific rather than a global manner. Different parts of the brain regulate the induction and onset of anesthesia. Induction is when the animal receiving general anesthesia goes from conscious to unconscious, while emergence is when the patient goes from unconscious to conscious. “We found that microglia can facilitate and stabilize the response to general anesthesia by modulating the neuronal network in a brain region-specific manner. This is mediated by the microglial P2Y12 receptor and downstream calcium signaling,” Peng said. . Because of this brain region-specific regulation, depletion of microglia not only delayed the time it took for the anesthesia to work (delayed induction), but also meant that the anesthesia wore off more quickly (early onset). “Our results also indicate that microglia contribute complexly and diversely to the orchestration of CNS function, rather than playing a discrete role in negative feedback control,” Peng said.
Looking ahead, the researchers want to understand more about microglial cells and how the P2Y12 receptor is related to neurological disorders. This receptor appears to be essential for a stable neuronal network and is suppressed in multiple neurological disorders. In addition, researchers will continue to learn how general anesthesia works. “Looking forward, we plan to continue dissecting the mechanism of general anesthesia and studying how microglia contribute to central nervous system (CNS) function,” said Yousheng Shu, who is also a professor at the University’s Institute for Translational Brain Research. Fudan. .
Other contributors are Yang He, Taohui Liu, Quansheng He, Wei Ke, Xiaoyu Li, Jinjin Du, Suixin Deng, Zhenfeng Shu, Jialin Wu, Baozhi Yang, Yuqing Wang, Ying Mao, Yanxia Rao, and Yousheng Shu.
STI2030-Major Projects, National Natural Science Foundation of China, “Shuguang Program” supported by Shanghai Education Development Foundation and Shanghai Municipal Education Committee, Shanghai Academic/Technology Research Officer Program, Innovative Research Group of Shanghai Local Higher University, Shanghai Municipal Science and Technology Major Project and ZJ Lab supported this research.
Source:
Journal Reference:
He, Y., et al. (2023). Microglia facilitate and stabilize the response to general anesthesia by modulating the neuronal network in a brain region-specific manner. eLife. doi.org/10.7554/eLife.92252.
