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

Abstract

Meningitic Escherichia coli 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 E. coli-induced CNS dysfunction. Here, by using in vivo and in vitro BBB models, we demonstrated that resveratrol treatment significantly inhibited meningitic E. coli 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. In vivo treatment of resveratrol decreased the production of inflammatory cytokines and improved the survival rate in mice challenged with meningitic E. coli. These findings collectively indicated that resveratrol could attenuate meningitic E. coli-induced CNS injury, which might constitute a new approach for future prevention and treatment of E. coli meningitis.