NLRP3 inflammasome activation increase IL1β levels and cause impairment cognitive in pneumococcal meningitis

Abstract

Pneumococcal meningitis is an important cause of morbidity and mortality worldwide, and the most common causative organism of community acquired bacterial meningitis in adults is Streptococcus pneumoniae. Studies have examined the role of inflammasomes in bacterial meningitis and demonstrated the NLR are also involved in the recognition of S. pneumoniae by the innate immune system. In this context, the aim of the present study was to evaluate the NLRP3 expression and IL1B levels in hippocamp and frontal cortex and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Where use male Wistar rats, the bacterial meningitis induction was performed under anaesthesia, the animals received intracisternal injection of 10 μL of artificial cerebrospinal fluid (CSF) as a placebo or an equivalent volume of S. pneumoniae suspension. At 18 hours we confirm the meningitis infection and the animals destined to the behavioral tests received antimicrobial treatment. For the 24 hours protocol the animals were divided into control (n = 6), meningitis (n = 6), after this time the hippocampus and prefrontal cortex were removed for evaluation of NLRP3 expression and levels of IL-1β. In the protocol for behavioral tests at 10 days, the animals were divided into control (n = 10), meningitis (n = 10). After the behavioral tests the animals were euthanized, and the hippocampal and prefrontal cortex structures removed for evaluation of NLRP3 expression and levels of IL-1β. The expression of NLRP3 was increased in both brain structures, of the meningitis group when compared to the control group. In the task of habituation to the open field, there were no differences in the groups in the training session. In the test session, there was a significant reduction in crosses and withdrawals in the control group demonstrating habituation memory in these groups. However, the meningitis group showed no difference between the training and test sessions, demonstrating impairment of habituation memory in this group. In the behavioral test of recognition of new objects, the animals of the meningitis group presented memory impairment of the object recognition, they did not use a significantly longer time exploring the new object, presenting loss of long-term memory. However, the animals in the control group had long-term memory between the test sessions compared to the training session. In the inhibitory avoidance task there was a difference between the training and test sessions in the control group and in the meningitis group there was no difference between the training and test sessions, demonstrating aversive memory impairment in these animals. NLRP3 expression at 10 days post-induction was increased in the hippocampus and prefrontal cortex of the meningitis group when compared to the control group. In conclusion, we showed that experimental meningitis model induced the NLRP3 inflamassome activation, increased the IL1B levels and impairment behaviours in rats.