Sevoflurane, the most commonly used inhaled
anesthetic in
pediatric anesthesia, has been reported to induce
cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated.
Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in
neurological disorders and aging models through anti-inflammatory activity. However, its effect on
sevoflurane-induced
cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of
resveratrol on
sevoflurane-induced
cognitive impairment. Six-day-old mice received
anesthesia with 3%
sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg
resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before
anesthesia.
Sevoflurane exposure significantly suppressed the expression of
Sirtuin 1 (
SIRT1) and activated microglia in hippocampi. Furthermore, the levels of
interleukin-6 (IL-6) and
tumor necrosis factor-α (TNF-α) were markedly increased after
sevoflurane exposure. Strikingly,
resveratrol pretreatment ameliorated
sevoflurane-induced
SIRT1 inhibition and microglial activation. Of note,
resveratrol reversed
sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing
mRNA level of clusters of differentiation 206 (CD206) and decreasing
mRNA levels of clusters of differentiation 86 (CD86) and suppressor of
cytokine signaling 3 (SOCS3). Consequently,
sevoflurane-induced
cognitive impairment in developing mice was ameliorated by
resveratrol pretreatment. Taken together, repeated
sevoflurane exposure to the developing brain resulted in
SIRT1 inhibition, NF-κB acetylation, and microglial activation.
Resveratrol pretreatment ameliorated
cognitive impairment in developing mice received
sevoflurane exposure by modulating SIRT1-NF-κB pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of
sevoflurane.