title: Sulforaphane improves outcomes and slows cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats.
abstract: Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague-Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18.
authors.affiliation: ChongQing Medical University, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: ChongQing Medical University, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.affiliation: ChongQing General Hospital, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: ChongQing Medical University, China.
authors.forename: Ling Yu
authors.initials: LY
authors.lastname: Li
authors.affiliation: ChongQing Medical University, China.
authors.forename: Yang Hao
authors.initials: YH
authors.lastname: Hou
authors.affiliation: ChongQing Medical University, China. Electronic address: 7461528@qq.com.
authors.forename: Fang Zhou
authors.initials: FZ
authors.lastname: Song
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D019607:Brassicaceae / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013454:Sulfoxides
chemical_list: D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D017879:Isothiocyanates; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; C573346:Nlrp3 protein, rat; D013454:Sulfoxides; D020170:Caspase 1; C016766:sulforaphane
keywords: Sulforaphane NLRP3 inflammasome cerebral ischemia/reperfusion