Abstract

Repeat sevoflurane exposure can cause developmental neurotoxicity while its underlying mechanism is still ambiguous. Contemporary research has increasingly highlighted the regulatory role of non-coding RNAs (ncRNAs) in the development of neurological diseases, particularly neurodegenerative conditions. However, the potential involvement of ncRNAs in sevoflurane-induced neurotoxicity remains poorly understood. In the current study, our comprehensive analysis of competing endogenous RNAs (ceRNAs) networks has identified circleRNA (circRNA) 2092 as a pivotal modulator in repetitive sevoflurane-mediated cognitive impairment, regulating microglia oxidative stress through the inhibition of microRNA miR-873a-5p and the promotion of Kelch-like ECH associating protein 1(KEAP1) expression. Notably, either knockdown of circRNA2092 and KEAP1 or administration of miR-873a-5p and Resveratrol (Oxidative stress inhibitor) could reverse the neurotoxicity of sevoflurane. Collectively, these findings demonstrate that repetitive sevoflurane exposure leads to long-term cognitive impairment in neonatal mice by aggravating microglial oxidative stress and neuroinflammatory response via the circRNA2092/miR-873a-5p/KEAP1 axis.