Abstract

Our previous studies have demonstrated that repeated exposure of neonatal rats to sevoflurane upregulates the expression of major histocompatibility complex class I and class II (MHC-I/MHC-II) in oligodendrocyte progenitor cells (OPCs) via the Kir4.1 channel, ultimately inhibiting OPC differentiation and reducing myelin formation. However, the therapeutic strategies for these antigen-presenting OPCs remain unclear. 2',3',4'-trihydroxyflavone (2-D08) has been shown to ameliorate demyelination through targeting Kir4.1, we therefore investigate whether it could prevent sevoflurane-induced antigen presentation switching in OPCs during early development. The results showed that 2-D08 markedly reduced sevoflurane-induced upregulation of MHC-I and MHC-II expression, as well as the secretion of IL-6 and IL-1β, in OPCs. This process ameliorated deficits in OPCs differentiation, ultimately restoring motor coordination impairments in rats. In vitro experiments also indicated that Kir4.1 knockdown OPCs exhibited a significant upregulation of MHC-I and MHC-II expression, accompanied by impaired differentiation, suggesting an essential role of Kir4.1 in regulating the antigen-presenting properties of OPCs. 2-D08 significantly upregulated Kir4.1 protein expression, and its protective effect against sevoflurane-induced antigen-presenting OPCs was abolished under Kir4.1 knockdown conditions. In conclusion, our study indicates that sevoflurane induces antigen presentation switching in OPCs through the activation of the Kir4.1 channel, an effect that can be ameliorated by 2-D08.

Key Points

• Sevoflurane exposure increases antigen presentation, disrupting OPC differentiation.
• MHC-I and MHC-II levels increased by 2-D08 with reduced IL-6 and IL-1β secretion in OPCs.