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Updated: Apr 22, 2026
A Ferret Model of Inflammation-sensitized Late Preterm Hypoxic-ischemic Brain Injury
Published on: November 19, 2019
Sevoflurane-induced neurotoxicity in neonatal mice is driven by microglial ferroptosis via MSTRG.7388-dependent
Qi Zhang1, Jiahui Ma2, Yi Gao3
1Postdoctoral Mobile Station of the Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, 050051, China; Department of Anesthesiology, Hebei Children's Hospital, Shijiazhuang City, Hebei Province, 050031, China.
Abstract:
Preclinical investigations have indicated that recurrent sevoflurane exposure induces long-term cognitive deficits in neonatal mice while the effects of inhalational anesthetics on children remain ambiguous. In the current study, Our comprehensive analysis of single-nucleus transcriptomics-guided competing endogenous RNA (ceRNA) networks revealed long-stranded ncRNA (lncRNA) MSTRG.7388 as a pivotal modulator in sevoflurane-mediated cognitive impairment, regulating microglial activation through the inhibition of microRNA miR-410-3p and the promotion of nuclear receptor coactivator 4 (NCOA4) expression. Furthermore, we elucidated that mutual binding of NCOA4 and stimulator of interferon genes (STING) dimers induced microglial ferroptosis independent of the ubiquitination pathway and long-term cognitive impairment in mice exposed to sevoflurane. Notably, either the knockdown of NCOA4 or the administration of Fe2+ scavengers (iron chelators) reversed these effects. Collectively, these findings demonstrate that repeated sevoflurane exposure leads to long-term cognitive impairment in neonatal mice by aggravating microglial ferroptosis via the MSTRG.7388/miR-410-3p/NCOA4/STING signaling axis.
Insights
Repeated sevoflurane exposure causes long-term cognitive deficits in neonatal mice by increasing microglial ferroptosis. This occurs through the MSTRG.7388/miR-410-3p/NCOA4/STING pathway, which can be reversed by blocking NCOA4 or using iron scavengers.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Recurrent sevoflurane exposure in neonates may cause long-term cognitive deficits.
- The precise mechanisms linking inhalational anesthetics to pediatric cognitive impairment are unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying sevoflurane-induced cognitive impairment in neonatal mice.
- To identify key regulatory pathways involved in sevoflurane neurotoxicity.
Main Methods:
- Single-nucleus transcriptomics and competing endogenous RNA (ceRNA) network analysis.
- Investigated the role of lncRNA MSTRG.7388, miR-410-3p, NCOA4, and STING in microglial ferroptosis.
- Utilized knockdown and iron chelator administration in mouse models.
Main Results:
- lncRNA MSTRG.7388 regulates microglial activation by inhibiting miR-410-3p and promoting NCOA4.
- NCOA4 and STING dimer binding induces microglial ferroptosis, independent of ubiquitination.
- Knockdown of NCOA4 or iron chelation reversed sevoflurane-induced cognitive impairment.
Conclusions:
- Sevoflurane-induced cognitive impairment in neonatal mice is mediated by microglial ferroptosis.
- The MSTRG.7388/miR-410-3p/NCOA4/STING signaling axis is a critical pathway in this process.
- Targeting this axis offers potential therapeutic strategies for anesthetic-induced neurotoxicity.
