J Neurochem. 2025 Jun;169(6):e70118. doi: 10.1111/jnc.70118.
ABSTRACT
Sevoflurane is widely used in pediatric anesthesia due to its rapid induction, minimal airway irritation, and stable hemodynamics. However, concerns have been raised regarding its potential adverse effects on cognition. Recent studies suggest that GluN2B-containing NMDA receptors play a key role in the memory deficits associated with sevoflurane exposure. In this study, we investigated whether the GluN2B small interfering peptide (GluN2B-sip) could protect against neurotoxicity induced by neonatal sevoflurane exposure. Our findings show that neonatal sevoflurane exposure leads to an increase in apoptosis-related proteins, long-term memory impairment, and reduced levels of synaptic proteins in the hippocampus of adolescent rats. GluN2B-sip partially restored synapse development and cognitive function. Together, these results suggest that GluN2B-sip mitigates sevoflurane-induced neurodegeneration and cognitive impairment in developing rats, providing a potential therapeutic strategy to prevent sevoflurane neurotoxicity. The Cdk5/GluN2B and Cdk5/CRMP2 signaling pathways may play central roles in this protective effect.
PMID:40501436 | DOI:10.1111/jnc.70118
