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

Da-Ming Sui,Jin-Bao Li,Xiao-Ming Deng,Wen-Jing Yi,Jun Wang,Xi-Ya Yu,Qun Xie,Jia-Feng Wang,Sahil Gupta

doi:10.1155/2016/1045657

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-1β, 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-1β. 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-1β 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-1β 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-1β axis in the microglia.

Highlights

Sepsis refers to the systemic inflammatory response by the immune system towards invading foreign pathogens
cecal ligation and puncture (CLP) mice treated with a high dose (30 mg/kg) of resveratrol had shorter latency periods at days 3 and 4 of training (P < 0.05), while those treated with a lower dose of resveratrol (10 mg/kg) exhibited shorter latency periods on the last day of training (P < 0.05)
Not surprisingly, our data demonstrated that resveratrol was protective against sepsis-associated encephalopathy (SAE) according to the spatial learning training and test, as well as the neuronal apoptosis in the hippocampus

Summary

Introduction

Sepsis refers to the systemic inflammatory response by the immune system towards invading foreign pathogens. This multipronged defense response is the third leading cause for death in the United States [1]. During this response, multiple organ failure has the potential to be elicited, where manifestation of brain dysfunction during sepsis can lead to sepsis-associated encephalopathy (SAE) [2, 3]. Majority of the treatments directed towards SAE patients are focused towards controlling the systemic spread of infection, while providing supportive therapy

Methods

Results

Conclusion