Novel insights into sevoflurane-induced developmental neurotoxicity mechanisms

<b>Aim:</b> This study explores Sevoflurane (Sevo)-induced neurotoxicity mechanisms in neonates through transcriptome sequencing and models. <b>Methods:</b> Seven-day-old mice were exposed to 3% Sevo, and hippocampal tissue was collected for analysis of differentially expressed lncRNAs and mRNAs compared with normal mice. MiR-152-3p was selected, and the interaction between H19, USP30, and miR-152-3p was explored in BV2 microglial cells and mouse hippocampal neurons. <b>Results:</b> Sevo disrupts mitochondrial autophagy via USP30 upregulation, exacerbating neurotoxicity and activating NLRP1 inflammasome-mediated inflammation. <b>Conclusion:</b> Sevo neurotoxicity is mediated through the H19/miR-152-3p/USP30 axis, implicating microglial regulation of neuronal pyroptosis. The study investigates the neurotoxicity of Sevoflurane (Sevo) in neonatal mice, focusing on the H19/miR-152-3p/USP30 signaling axis. Utilized both <i>in vitro</i> (BV2 microglial cells) and <i>in vivo</i> (neonatal mice) models to explore the role of H19, miR-152-3p, and USP30 in Sevo-induced neurotoxicity. Sevo exposure leads to significant overexpression of H19 in the hippocampal tissues of neonatal mice, contributing to neurotoxicity by upregulating USP30. Demonstrated that H19 competitively binds to miR-152-3p, which upregulates USP30, inhibiting mitophagy and promoting microglial cell activation. USP30 upregulation leads to the activation of the NLRP1 inflammasome in microglial cells, resulting in the release of inflammatory cytokines IL-1β and IL-18, exacerbating neuronal pyroptosis. Silencing USP30 mitigates Sevo-induced neurotoxicity by enhancing mitophagy, reducing microglial activation, and decreasing inflammatory responses. The H19/miR-152-3p/USP30 axis is a key mediator in Sevo-induced developmental neurotoxicity, offering insights into potential therapeutic targets for mitigating neurotoxic effects.