Resveratrol Defends Blood-brain Barrier Integrity in Experimental Autoimmune Encephalomyelitis Mice

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, anti-oxidative 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 occluden-1, occludin, ICAM-1 and VCAM-1. Inflammatory factors iNOS, IL-1b and arginase1 were evaluated by qPCR, and IL-10 by ELISA. NADPH oxidase levels were evaluated by qPCR, and its activity was analyzed by lucigenin-derived chemiluminiscence. 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 pro-inflammatory 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 NOX-2 and NOX-4 in the brain and suppressed NADPH activity. Resveratrol ameliorates the clinical severity of MS through maintaining the BBB integrity in EAE mice.

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