Fig. 11

The pathogenesis diagram of the SIN. Prolonged anesthesia by sevoflurane in rats triggers cognitive impairment, anxiety-like behaviors, neuroinflammation, and complement activation. We observed critical microglial synaptic elimination and dendritic spines loss driven by complement and neuroinflammation in the hippocampus after prolonged anesthesia. There was a remarkable increase in phagocytic and chemotactic microglia, accumulation of C1qa on synapses, and downregulation of synaptic proteins and genes in the hippocampus. Activated microglia with a specific morphological structure and phenotype induce neuroinflammation and complement activation, engulf synapses, and cause synaptic loss. Depletion of microglia by PLX3397 treatment blocks this process. Furthermore, inhibiting neuroinflammation with meloxicam and C1q neutralization also rescued synaptic loss