Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1ß Axis in Microglia.

ABSTRACT

Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1ß, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1ß. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1ß cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1ß cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1ß axis in the microglia.