Sodium aescinate improve behavioral performance by inhibiting dorsal raphe nucleus NLRP3 inflammasome in Post-traumatic stress disorder Rat Model

Growing evidence suggest that NLRP3 inflammasome activation in hippocampus and amygdala is involved in the pathophysiology of PTSD. Our previous studies have demonstrated that apoptosis of dorsal raphe nucleus (DRN) contributes to the pathological progression of PTSD. Recent studies by others have shown that in brain injury sodium aescinate (SA) has a protective effect on neurons by inhibiting inflammatory response pathways, thereby relieving symptoms. Here, we extend the therapeutic effects of SA to PTSD rats. We found that PTSD was associated with significant activation of the NLRP3 inflammasome in DRN, whereas administration of SA significantly inhibited DRN NLRP3 inflammasome activation and reduced DRN apoptosis level. SA also improved learning and memory ability and reduced anxiety and depression level in PTSD rats. In addition, NLRP3 inflammasome activation in DRN of PTSD rats impaired mitochondria function by inhibiting ATP synthesis and increasing ROS production, whereas SA can effectively reverse the pathological progression of mitochondria. We recommend SA as a new candidate for the pharmacological treatment of PTSD. •SA improved learning and memory ability and reduced anxiety and depression level in PTSD rats.•SA reduced DRN apoptosis level in PTSD rats.•SA inhibited activation of DRN NLRP3 inflammasome PTSD rats.•SA administration reduced mitochondrial ROS production and increased mitochondrial ATP synthesis in DRN of PTSD rats.