title: Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia.
abstract: Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1β, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1β. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1β cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1β cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1β axis in the microglia.
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China; Department of Anesthesiology, Chengdu Military General Hospital, 270 Tianhui Road, Chengdu 610083, China.
authors.forename: Da-ming
authors.initials: DM
authors.lastname: Sui
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Yi
authors.affiliation: The Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1T8; Department of Surgery, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, ON, Canada M5B 1W8.
authors.forename: Sahil
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Xi-ya
authors.initials: XY
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Jin-bao
authors.initials: JB
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Jia-feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Deng
mesh_terms: D000818:Animals; D002460:Cell Line; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D000077185:Resveratrol; D065166:Sepsis-Associated Encephalopathy / Q000188:drug therapy* / Q000378:metabolism*; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D013267:Stilbenes; D000077185:Resveratrol