Resveratrol Attenuates Meningitic <i>Escherichia coli</i>-Mediated Blood–Brain Barrier Disruption

Abstract

Meningitic <i>Escherichia coli</i> can infiltrate the central nervous system (CNS), consequently increasing the levels of proinflammatory cytokines and chemokines and deteriorating the integrity of the blood-brain barrier (BBB). Resveratrol has emerged in recent years as a compound with antioxidant and anti-inflammatory properties. However, it is still unknown how resveratrol affects meningitic <i>E. coli</i>-induced CNS dysfunction. Here, by using <i>in vivo</i> and <i>in vitro</i> BBB models, we demonstrated that resveratrol treatment significantly inhibited meningitic <i>E. coli</i> invasion of the BBB, protected the integrity of the BBB, and reduced neuroinflammation and lethality. In mechanism, resveratrol inhibited bacterial penetration of the BBB by attenuating the upregulation of caveolin-1 (CAV-1), a class of lipid rafts maintaining endothelial cell function. Resveratrol treatment also maintained BBB permeability by suppressing the ERK1/2-VEGFA signaling cascade. <i>In vivo</i> treatment of resveratrol decreased the production of inflammatory cytokines and improved the survival rate in mice challenged with meningitic <i>E. coli</i>. These findings collectively indicated that resveratrol could attenuate meningitic <i>E. coli</i>-induced CNS injury, which might constitute a new approach for future prevention and treatment of <i>E. coli</i> meningitis.