Sevoflurane aggravated neuroinflammation and oxidative stress in neonatal mice by modulating microglia phenotype via circRNA2092/miR-873a-5p/KEAP1

  • Neurotoxicology. 2026 Mar:113:103410. doi: 10.1016/j.neuro.2026.103410.
Yanan Li  1 ,  Juan Du  2 ,  Jiajie Zhang  3 ,  Zhenzhen Cai  3 ,  Lei Shi  4 ,  Jia Liang  5 ,  Qi Zhang  6
Affiliations
  • 1. Department of Anesthesiology, The Third Hospital of Hebei Medical University, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China.
  • 2. Department of Thoracic Surgery, Hebei Children's Hospital, Shijiazhuang, Hebei 050031, China.
  • 3. Graduate School of Hebei Medical University, Shijiazhuang, Hebei 050011, China; Department of Anesthesiology, Hebei Children's Hospital, Shijiazhuang, Hebei 050031, China.
  • 4. Department of Anesthesiology, Hebei Children's Hospital, Shijiazhuang, Hebei 050031, China; Hebei Provincial Clinical Research Center for Child Health and Disease, Shijiazhuang, Hebei 050031, China. Electronic address: [email protected].
  • 5. Beijing Institute of Biological Products Co., Ltd, Beijing 102699, China; Pathology Teaching and Research Office of Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: [email protected].
  • 6. Department of Anesthesiology, Hebei Children's Hospital, Shijiazhuang, Hebei 050031, China; Hebei Provincial Clinical Research Center for Child Health and Disease, Shijiazhuang, Hebei 050031, China. Electronic address: [email protected].
PMID: 41759746 DOI: 10.1016/j.neuro.2026.103410
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.

Keywords
CircRNA; Cognitive dysfunction; KEAP1; Nrf2; Oxidative stress; Sevoflurane.
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