Effects of MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy

Abstract

Objective To investigate the effects of Nod-like receptor protein 3 inhibitor MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE). Methods Ninety adult male C57BL/6 mice were randomly (random number) divided into three groups: the sham + saline group (n=20, sham group), CLP + saline group (n=35, CLP group), and CLP + MCC950 group (n=35, MCC950 group). SAE mouse model was established by cecal ligation and puncture (CLP) surgery. Saline (10 mL/kg) or MCC950 (10 mg/kg) was intraperitoneally injected 30 min before surgery and on day 1, 2, 4 and 6 after surgery according the grouping. Seven days after surgery, six mice were taken from each group. Western blot was used to detect the hippocampal content of NLRP3, apoptosis-associated speck-like protein (ASC), interleukin-1β (IL-1β) and IL-18. The number of NLRP3-positive cells in CA1 region were detected by immunohistochemical analysis. The remaining mice in each group were used for open field and fear conditioning tests 14 days after surgery. One-way analysis of variance was used for inter-group comparison, and SNK-q test was used for pairwise comparison. A P value <0.05 was considered statistically significant. Results Compared the MCC950 group with the CLP group, the freezing time of context test was significantly increased [(137±21) s vs (84±15) s, P=0.013 ], the hippocampal content of NLRP3, IL-1β and IL-18 were significantly reduced (P 0.05). Conclusions MCC950 administration can improve cognitive function in a mouse model of SAE, which is probably due to the inhibition of NLRP3 inflammasome and downstream inflammatory cytokines IL-1β and IL-18. Key words: Sepsis-associated encephalopathy; Cognitive function; Neuroinflammation; NLRP3 inflammasome; Interleukin-1β; Interleukin-18