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.
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan 450046, China.
ACS Infect Dis. 2021 Apr 9;7(4):777-789. doi: 10.1021/acsinfecdis.0c00564. Epub 2021 Mar 16.
Meningitic 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 -induced CNS dysfunction. Here, by using and BBB models, we demonstrated that resveratrol treatment significantly inhibited meningitic 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. treatment of resveratrol decreased the production of inflammatory cytokines and improved the survival rate in mice challenged with meningitic . These findings collectively indicated that resveratrol could attenuate meningitic -induced CNS injury, which might constitute a new approach for future prevention and treatment of meningitis.
脑膜炎奈瑟菌可渗透中枢神经系统（CNS），从而增加促炎细胞因子和趋化因子的水平，并损害血脑屏障（BBB）的完整性。白藜芦醇近年来作为一种具有抗氧化和抗炎特性的化合物而备受关注。然而，白藜芦醇如何影响脑膜炎奈瑟菌引起的中枢神经系统功能障碍仍不清楚。在这里，我们通过使用 和 BBB 模型，证明白藜芦醇治疗可显著抑制脑膜炎奈瑟菌对 BBB 的侵袭，保护 BBB 的完整性，并减轻神经炎症和致死率。在机制上，白藜芦醇通过减弱脂筏维持内皮细胞功能的一种小窝蛋白-1（CAV-1）的上调来抑制细菌穿透 BBB。白藜芦醇治疗还通过抑制 ERK1/2-VEGFA 信号级联来维持 BBB 的通透性。白藜芦醇处理可减少炎症细胞因子的产生，并提高脑膜炎奈瑟菌感染小鼠的存活率。这些发现共同表明，白藜芦醇可减轻脑膜炎奈瑟菌引起的中枢神经系统损伤，这可能为未来预防和治疗脑膜炎提供新方法。
