title: Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice.
abstract: The mouse autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), is primarily characterized as dysfunction of the blood-brain barrier (BBB). Resveratrol exhibits anti-inflammatory, antioxidative, and neuroprotective activities. We investigated the beneficial effects of resveratrol in protecting the integrity of the BBB in EAE mice and observed improved clinical outcome in the EAE mice after resveratrol treatment. Evans blue (EB) extravasation was used to detect the disruption of BBB. Western blot were used to detected the tight junction proteins and adhesion molecules zonula occludens-1 (ZO-1), occludin, ICAM-1, and VCAM-1. Inflammatory factors inducible nitric oxide synthase (iNOS), IL-1β, and arginase 1 were evaluated by quantitative RT-PCR (qPCR) and IL-10 by ELISA. NADPH oxidase (NOX) levels were evaluated by qPCR, and its activity was analyzed by lucigenin-derived chemiluminescence. Resveratrol at doses of 25 and 50 mg/kg produced a dose-dependent decrease in EAE paralysis and EB leakage, ameliorated EAE-induced loss of tight junction proteins ZO-1, occludin, and claudin-5, as well as repressed the EAE-induced increase in adhesion proteins ICAM-1 and VCAM-1. In addition, resveratrol suppressed the EAE-induced overexpression of proinflammatory transcripts iNOS and IL-1β and upregulated the expression of anti-inflammatory transcripts arginase 1 and IL-10 cytokine in the brain. Furthermore, resveratrol downregulated the overexpressed NOX2 and NOX4 in the brain and suppressed NADPH activity. Resveratrol ameliorates the clinical severity of MS through maintaining the BBB integrity in EAE mice.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; and.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; and.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; and.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Fu
authors.affiliation: Department of Emergency, Xingtai People's Hospital, Xingtai, Hebei, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; and.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; and ligguoer@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D013267:Stilbenes; D000077185:Resveratrol
keywords: blood-brain barrier; encephalomyelitis; multiple sclerosis; resveratrol