Neuroglobin alleviates the neurotoxicity of sevoflurane to fetal rats by inhibiting neuroinflammation and affecting microglial polarization.

Sevoflurane, a commonly used inhaled anesthetic, causes endogenous apoptosis in fetal rats. Microglia polarization is associated with inflammation, and the IL-10/STAT3/SOCS3 pathway is involved in this process. Neuroglobin (Ngb) is a neuroprotective protein which exhibits an anti-inflammatory effect. The purpose of this study was to investigate whether neurotoxicity induced by sevoflurane exposure in prenatal rats correlates with neuroinflammation and microglia polarization and whether Ngb can moderate this response. We found that exposure to sevoflurane on the 20th day of gestation (G20) induced discernable inflammation in postnatal day 0 (P0) rats, promoted M1 polarization of microglia, and inhibited M2 polarization. Hemin-mediated Ngb elevation inhibited sevoflurane-induced neuroinflammation. Additionally, elevated Ngb inhibited M1 polarization and promoted M2 polarization of microglia. We also found that elevated Ngb could alleviate the effect of sevoflurane on the expression of Interleukin-10 (IL-10), phosphorylated-signal transduction and activators of transcription 3 (P-STAT3), and suppressor of cytokine signaling 3 (SOCS3). Furthermore, we found that elevated Ngb ameliorated the effects of sevoflurane on long-term exploratory behavior and learning and memory in the offspring. Our results show that Ngb alleviates the neurotoxicity of sevoflurane to fetal rats by inhibiting neuroinflammation and affecting microglial polarization, a process which may involve the IL-10/STAT3/SOCS3 pathway.