Voluntary exercise attenuates mice anxiety after traumatic brain injury via inhibiting NLRP3 inflammasome activation

Abstract

Background: Psychological disorders, particularly the anxiety after traumatic brain injury (TBI) have received great attention both in clinical practice and experimental investigation. New therapeutic strategies are urgently required nowadays to improve mental condition of TBI patients. Neuroinflammation is the typical adaptive response that played important roles in psychiatric illness after brain tissue damage. Therefore, the immune-targeted therapy has aroused attention. Voluntary exercise has been considered as the most essential rehabilitative intervention following TBI. However, there were some experiments showed opposite effects, which varies with different time windows. Whether and when the voluntary exercise should be taken after TBI remain to be defined. The aim of the current study was to elucidate whether in-time voluntary exercise could improve the neurological recovery and reduce the anxiety of TBI mice by inhibiting the neuroinflammation via attenuating the activation of NLRP3 inflammasome.Methods: Kunming mice (8 weeks) were subjected to TBI and randomly divided into 4 groups One week voluntary wheel running (VWR) was applied to TBI mice soon after trauma - at 2nd day after injury. The neurofunction of TBI mice was detected by neurological severity score (NSS) and beam walking assay. Anxiety behavior was evaluated by open-field (OF) test and elevated plus maze (EPM) test. The cellular inflammatory signal, including IL-12, IFN-γ, CCL2, IL-10 and TGF-β, as well as the activation of microglia and NLRP3 inflammasome in the perilesional cortex were investigated.Results: After one week VWR, neurological function recovery was enhanced while the anxiety behavior of TBI mice was significantly eased. Accompanied with this, anti-inflammatory signaling, IL-10 in particular, greatly elevated. NLRP3 expression, caspase-1 activation and pro-inflammatory cytokines IL-1β/ IL-18 secretion were significantly inhibited. All these alterations were consistent with reduced microglia activation in the perilesional site and positively correlated with the weaken of anxiety behavior.Conclusion: In-time VWR could be a high potential therapeutic strategy for neuropsychiatric disorders following TBI by targeting neuroinflammation.