1. Academic Validation
  2. Resveratrol Attenuates Meningitic Escherichia coli-Mediated Blood-Brain Barrier Disruption

Resveratrol Attenuates Meningitic Escherichia coli-Mediated Blood-Brain Barrier Disruption

  • ACS Infect Dis. 2021 Apr 9;7(4):777-789. doi: 10.1021/acsinfecdis.0c00564.
Ruicheng Yang 1 Yujin Lv 1 2 Ling Miao 1 Huipeng Zhang 1 Xinyi Qu 1 Jiaqi Chen 1 Bojie Xu 1 Bo Yang 1 Jiyang Fu 1 Chen Tan 1 3 4 Huanchun Chen 1 3 4 Xiangru Wang 1 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 2 College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan 450046, China.
  • 3 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei 430070, China.
  • 4 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei 430070, China.
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.

Keywords

Escherichia coli meningitis; blood−brain barrier; neuroinflammation; permeability; resveratrol.

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