Escitalopram alleviate depression in rats after stroke by decreasing serum levels of interleukin-18 / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of escitalopram on the levels of serum proinflammatory cytokine interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),and IL-18 in a rat model of poststroke depression (PSD).Methods Twenty-four male Sprague-Dawley rats were randomly allocated into sham operation,middle cerebral artery occlusion (MCAO),PSD and escitalopram groups (n =6 in each group).A model of MCAO was induced by the intraluminal suture method,and on this basis,a PSD model was induced by combining with chronic unpredictable mild stress (CUMS) plus lonely upbringing.The rats of both the sham operation group and the MCAO group were neither CUMS nor lonely upbringing,and in the PSD group they were both CUMS and lonely upbringing.The escitalopram group was given escitalopram intervention (10 mg/kg · d,intraperitoneal injection for 3 weeks) at the beginning of CUMS and lonely upbringing.At baseline and on day 7,14 and 21 after CUMS,sucrose solution consumption and wilderness trials were used to assess depression-like behavior.Enzyme-linked immunosorbent assay was used to detect the levels of serum proinflammatory cytokines IL-6,TNF-α and IL-18 on day 21 after CUMS.Results On day 21 after CUMS,the scores of weight,sucrose solution consumption,vertical test and the distance of horizontal activities were all significantly decreased and shortened compared to those of the sham operation group and the MCAO group (all P＜0.01).The weight,sucrose solution consumption,and the distance of horizontal activities of the escitalopram group were significantly increased compared to those of the PSD group (P ＜0.05 or P ＜0.01).On day 22 after CUMS,the serum IL-18 level of the PSD group was increased significantly compared to that of the sham operation group and the MCAO group (P ＜ 0.05 or P ＜ 0.01).The serum IL-18 level of the escitalopram group was decreased significantly compared to that of the PSD group (P ＜0.05).However,there were no significant differences in the levels of IL-6 and TNF-α among all the groups.Correlation analysis showed that on day 22 after CUMS,the serum IL-18 level and sucrose solution consumption (r =-0.415,P =0.044),the distance of horizontal activities in the wilderness trials (r =-0.508,P =0.011) showed a significant negative correlation,however,they did not have significant correlation with the vertical score (r =-0.390,P=0.059) and the body weight (r=-0.216,P=0.311).Conclusions The serum IL-18 level is increased significantly in the PSD rat models.Escitalopram can significantly decrease the serum IL-18 level and improve depression-like behavior of the PSD rats,suggesting that IL-18 may play a role in the pathogenesis of PSD.