The figure summarizes the main findings of this study. **he et al.， elife， 2023
While this may come as a surprise to the millions of people who undergo general anesthesia for medical procedures each year, the biological mechanisms by which different anesthetics block consciousness are still not fully understood. However, researchers may be one step closer after discovering how small immune cells in the brain, called microglia, are affected by general anesthesia.
The study was published in eLife**.
We found that microglia play an important role in regulating the body's response to general anesthesia. Microglia are important immune cells in the central nervous system (CNS) and play a key role in central nervous system function and dysfunction," said Bo Peng, a professor at the Institute of Brain Translational Research at Fudan University in Shanghai, China.
Previous studies of microglia have shown that cells behave differently under anesthesia, but this study is the first to demonstrate how microglia regulate neuronal activity in a region-specific manner in the brain and play a key role in how anesthesia works.
First glimpses of how microglia affect anesthetic effects were inadvertently observed in other studies, which were then confirmed by additional testing. Induce microglial depletion in mice by blocking colony-stimulating factor 1 receptor (CSF1R) signaling.
When microglia are killed by a CSF1R inhibitor called PLX5622, they are highly resistant to anesthesia. This resistance to anesthesia was observed with four different types of anesthesia and two different receptors and confirmed by electroencephalogram (EEG) and electromyography (EMG) measurements.
Microglia also regulate brain network activity in a region-specific manner, rather than in a generic way. Different parts of the brain regulate anesthesia induction and appearance. Induction is the transformation of an animal under general anesthesia from conscious to unconscious, whereas arousal is the change of the patient from unconscious to conscious.
We found that microglia can facilitate and stabilize responses to general anesthesia by modulating neuronal networks in a brain region-specific manner. This is mediated by microglial p2y12 receptors and their downstream calcium signaling," Peng said.
As a result of this region-specific regulation of the brain, microglial depletion not only delays the time it takes for anesthesia to work (delayed induction), but also means that anesthesia subsides more quickly (early onset).
Our findings also suggest that microglia are complex and diverse in helping to coordinate central nervous system function, rather than indiscriminately playing a role in negative feedback control," Peng said.
Going forward, researchers hope to learn more about microglia and the relationship between p2y12 receptors and neurological disorders. This receptor is essential for stable neuronal networks and is inhibited in a variety of neurological disorders.
In addition, the investigators will continue to understand how general anesthesia works. "Going forward, we plan to continue to dissect the mechanism of general anesthesia and study how microglia contribute to central nervous system (CNS) function," said Shu Yousheng, a professor at Fudan University's Institute for Translational Brain Research.
More information: Yang He et al., Microglia facilitate and stabilize responses to general anesthesia by modulating neuronal networks in a brain region-specific manner, eLife (2023). doi： 10.7554/elife.92252