While millions worldwide undergo general anesthesia annually for various medical interventions, the intricate biological processes underpinning how different anesthetics induce unconsciousness remain elusive. A recent study published in eLife suggests that microglia, minute immune cells within the brain, might hold pivotal clues in unraveling this mystery.
Bo Peng, a distinguished professor at Fudan University's Institute for Translational Brain Research in Shanghai, emphasized, “Our findings illuminate the pivotal role of microglia in modulating the body's reaction to general anesthesia. These specialized immune cells are integral to the central nervous system's functionality and malfunctions.”
Although prior research hinted at alterations in microglial behavior during anesthesia, this investigation uniquely elucidates their role in modulating neuronal activity in a brain-specific context, underscoring their significance in anesthesia mechanisms. Serendipitously, during unrelated experiments, researchers observed the impact of microglial depletion in mice, achieved by inhibiting the colony-stimulating factor 1 receptor (CSF1R) signaling.
Notably, administering a CSF1R inhibitor, PLX5622, to eliminate microglia resulted in pronounced anesthesia resistance across four distinct types and two varied receptors. This phenomenon was corroborated through sophisticated neurophysiological assessments using electroencephalography (EEG) and electromyography (EMG).
Further insights revealed that microglia exert region-specific regulatory influences on brain network activity, modulating both anesthesia induction, transitioning from consciousness to unconsciousness, and emergence, the return to consciousness. Peng elucidated, “Microglia's role in facilitating and stabilizing anesthesia responses hinges on the microglial P2Y12 receptor and subsequent calcium signaling pathways.”
Interestingly, the absence of microglia not only protracted anesthesia onset but also expedited its cessation, highlighting their nuanced contributions to central nervous system (CNS) functionality rather than merely serving as passive feedback regulators.
Looking forward, the scientific community aims to delve deeper into understanding microglial intricacies, particularly exploring the P2Y12 receptor's implications in neurological disorders characterized by unstable neuronal networks. Yousheng Shu, another eminent professor at Fudan University's Institute of Translational Brain Research, affirmed their commitment to further dissecting general anesthesia mechanisms and comprehending microglia's multifaceted roles within the CNS.
Source: Fudan University