Interleukin-18 Involved Mice Model Of Post-stroke Depression And Its Mechanisms

Objective:Post-stroke depression is a group of post-stroke mental disorders with a high incidence of morbidity.Their onset may be insidious,while has a significant impact on the quality of life of patients.In this study,we explored a series of studies to determine whether interleukin-18(IL-18)levels in the brain of post-stroke depression mice increase,and whether IL-18 can induce post-stroke depression in mice.IL-18 plays an important role in the pathogenesis of post-stroke depression in mice,and gives interventions to provide guidance for the treatment of patients with post-stroke depression.Methods: Male ICR mice weighing 28-30 g were randomly divided into sham group,sham + stress group,ischemia/reperfusion(I/R)group,and ischemia/reperfusion + stress(SIR)group.In the SIR group,a mouse model of post-stroke depression was established.First,behavioral experiments were performed to assess the post-stroke depression model of mice,then take the ischemic brain tissue,and use Western blot method to detect changes in the amount of IL-18 protein expression in each group.Immunohistochemistry(DAB)staining was performed to assess the distribution of IL-18 protein distribution in post-stroke depression mice brain.Immunofluorescence staining was used to locate which cell in the brain secrete IL-18.Stereotaxic injection of mouse recombinant IL-18 protein into different brain regions,TST and FST were performed to assess whether mice were induced depression-like behavior by IL-18.Stereotaxic injection of IL-18 binding protein(IL-18BP)to observe its effect on post-stroke depression in mice therapeutic efficacy.Bumetanide is NKCC1 receptor antagonist,was used to assess the therapeutic effect of bumetanide on depression-like mice induced by stereotaxic injection of IL-18,the interaction between IL-18 R and NKCC1 was detected by coimmunoprecipitation(CO-IP).Results: Compared with Sham group,the content of IL-18 protein in SIR group began to increase on the 1st day of modeling and peaked on 3rd and 7th day,and began to decrease on the 14 th day.Immunofluorescence staining showed that IL-18 was colocalized with microglia,immunohistochemical staining showed that IL-18 exists in the SIR mouse ischemic hemisphere cortex,striatum,amygdala.While stereotaxic injection recombinant IL-18 into amygdala can induce significant depression-like behavior in mice.IL-18 BP can improve the depression behavior in SIR mice,coimmunoprecipitation showed that there is interaction between NKCC1 protein and IL-18 R and given NKCC1 inhibitor,bumetanide,reversed well the depressive behavior of mice induced by IL-18.Conclusions: This study demonstrated that IL-18 increased in the brain of poststroke depression model mice and played an important role in the development of poststroke depression.The content of IL-18 in brain of post-stroke depression mice peaked at about 1 week,with the depression-like behavior appear.Injection of recombinant IL-18 to the mouse amygdala can induce depression-like behavior in mice,and the biological effects of blocking the NKCC1 receptor with bumetanide can significantly improve IL-18-induced depression-like behavior of mice,suggesting that IL-18 may be a potential target for the treatment of post-stroke depression,providing a new idea for the treatment of post-stroke depression.