Sevoflurane induces long-term memory impairment and increases MeCP2 phosphorylation in developing mice

Sevoflurane is the most widely used volatile anesthetic in pediatric anesthesia. Some pediatric plastic surgery procedures (such as cleft lip repair, the repair of brachial plexus injury, etc.) may require multiple operations, requiring some children to repeatedly inhale this anesthetic. Evidence has suggested that sevoflurane may cause neuronal deficiency. We investigated the long-term effects of sevoflurane use and possible mechanisms underlying neurodegeneration induced by repeated sevoflurane exposure in the developing brain in the present study. Postnatal day 7 (P7) C57BL/6 mice were randomly exposed to either 1.5% sevoflurane or air control for 2 hours/day on 5 consecutive days. Methyl-CpG island binding protein 2 (MeCP2) phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were measured by western blotting. Seven weeks after sevoflurane exposure, a fear conditioning test was used to evaluate associative learning processes. Repeated exposure to 1.5% sevoflurane resulted in increased MeCP2 phosphorylation and decreased BDNF expression in the hippocampus. This study demonstrates that P7 mice exposed to 1.5% sevoflurane for 2 hours on 5 consecutive days have significant contextual learning and memory impairment after 7 weeks. These data suggest that repeated sevoflurane exposure may cause neurotoxicity in the developing brain by increasing MeCP2 phosphorylation and decreasing BDNF expression in the hippocampus.