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-alpha (TNF-alpha) 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-kappa B acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1NF-kappa B pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane. (C) 2020 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of China [81400882, 81771159, 81571047, 81974160, 81500982]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Anesthesiol, Wuhan, Hubei, Peoples R China
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Anesthesiol, Wuhan, Hubei, Peoples R China[*1]1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
推荐引用方式(GB/T 7714)：
Tang Xiao Le,Wang Xuan,Fang Gang,et al.Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice[J].JOURNAL OF NUTRITIONAL BIOCHEMISTRY.2021,90:doi:10.1016/j.jnutbio.2020.108579.
APA：
Tang, Xiao Le,Wang, Xuan,Fang, Gang,Zhao, Yi Lin,Yan, Jing...&Li, Shi Yong.(2021).Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice.JOURNAL OF NUTRITIONAL BIOCHEMISTRY,90,
MLA：
Tang, Xiao Le,et al."Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice".JOURNAL OF NUTRITIONAL BIOCHEMISTRY 90.(2021)
