title: Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice.
abstract: Although the underlying mechanisms of isoflurane-induced cognitive impairments remain largely to be determined, neuronal inflammation and apoptosis are thought to be major contributors. Resveratrol is a naturally available herbal compound for the treatment of inflammatory and neurodegenerative diseases. We therefore aimed to investigate the effects of resveratrol on the isoflurane-induced cognitive impairments and the associated hippocampal inflammation responses and neuronal apoptosis in the aged mice. Fifteen-month-old male C57BL/6 mice received 2 h of 1.5 % isoflurane or oxygen exposure 24 h after the intraperitoneal injection of resveratrol or saline daily for 7 consecutive days. Here, we showed that the isoflurane anesthesia decreased the freezing time to context significantly at 48 h after the isoflurane exposure in the fear conditioning test. The hippocampal levels of IL-1β, TNF-α, NLRP3, cleaved caspase-3, and Bax increased significantly while the hippocampal levels of IkBα and Bcl-2 decreased significantly at 6 and/or 48 h after the isoflurane anesthesia. All these effects induced by isoflurane were attenuated by resveratrol pretreatment. However, the isoflurane anesthesia had no significant effect on the hippocampal Sirt1. In conclusion, our results suggest that resveratrol attenuates the hippocampus-dependent cognitive impairment induced by isoflurane anesthesia through its anti-inflammation and anti-apoptosis effects in aged mice.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Mai-Tao
authors.initials: MT
authors.lastname: Zhou
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhou
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000367:Age Factors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D046352:Freezing Reaction, Cataleptic; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007530:Isoflurane / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D007530:Isoflurane; D056564:Sirtuin 1; D000077185:Resveratrol