How Microglia Impact the Effectiveness of General Anesthesia

A new study helps explain the mystery of how general anesthesia impacts consciousness by examining the role of microglia. The study, conducted by Bo Peng and his team at Fudan University in Shanghai, reveals that microglia, crucial immune cells in the central nervous system, play a key role in regulating the body's response to general anesthesia. This research, published in eLife, represents a significant step toward understanding the intricate mechanisms involved in the response to anesthesia.

In the study, microglia depletion was induced in mice by blocking the colony-stimulating factor 1 receptor (CSF1R) signaling. When microglia were killed with a CSF1R inhibitor called PLX5622, there was a 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 regulate brain network activity in a region-specific manner instead of a universal manner. Different parts of the brain regulate anesthesia induction and emergence. (Induction is when the animal receiving general anesthesia goes from consciousness to unconsciousness, while emergence is when the patient goes from unconsciousness to consciousness.) “We identified that microglia can facilitate and stabilize the response to general anesthesia via modulating the neuronal network in a brain region-specific manner. This is mediated by the microglial P2Y12 receptor and its downstream calcium signaling,” said Peng. Because of this brain region-specific regulation, microglial depletion not only delayed how long it took for anesthesia to work (delayed induction), but it also meant the anesthesia wore off faster (early emergence). “Our results also indicate that microglia sophisticatedly and diversely contribute to orchestrating the CNS function, rather than play an indiscriminate role of negative feedback control,” said Peng.

The P2Y12 receptor on microglia emerged as a focal point, influencing stable neuronal networks crucial for anesthesia effectiveness. Depletion of microglia not only delayed anesthesia induction but also led to faster emergence. This nuanced regulation challenges the conventional view of microglia as simple negative feedback controllers. Looking forward, researchers aim to delve deeper into the implications of the P2Y12 receptor in neurological disorders and continue dissecting the intricate mechanisms of general anesthesia to better comprehend the role of microglia in central nervous system function.