深部脑磁刺激改善大鼠卒中后抑郁样行为

Deep Brain Magnetic Stimulation Improves Depression-like Behavior after Stroke in Rats

目的:探讨深部脑磁刺激(DMS)对卒中后抑郁(PSD)模型大鼠抑郁样行为的治疗作用及其可能机制。方法:糖水偏好实验和旷场实验筛选42只正常的雄性成年SD大鼠,随机分为假手术组(Sham组,n=6)、卒中组(Stroke组,n=12)、卒中后抑郁组(PSD组,n=12)、深部脑磁刺激治疗组[(PSD+DMS)组,n=12];后3组颈总动脉线栓再灌注法构建脑缺血模型;假手术组只分离颈总动脉不结扎;PSD组和(PSD+DMS)组接受3周慢性温和应激制备PSD模型;(PSD+DMS)组每天接受40 min的40 Hz深部脑磁刺激治疗,共2周。旷场实验检测各组大鼠运动功能和焦虑样行为;糖水偏好实验检测各组大鼠快感缺失抑郁样行为;免疫荧光染色检测各组大鼠前额叶小胶质细胞激活标志物Iba-1的表达水平;蛋白质免疫印迹技术检测各组大鼠前额叶小胶质细胞激活阳性蛋白CD11b及炎性因子IL-1β和TNF-α的表达。结果:(PSD+DMS)组大鼠抑郁样行为较PSD组明显好转。卒中组大鼠前额叶小胶质细胞激活增加,炎性因子IL-1β和TNF-α的蛋白表达升高,PSD组大鼠前额叶小胶质细胞激活进一步增加,炎性因子IL-1β和TNF-α的蛋白表达进一步升高。(PSD+DMS)组大鼠前额叶小胶质细胞激活减少,炎性因子IL-1β和TNF-α的蛋白表达降低。结论:DMS治疗可有效地改善PSD大鼠的抑郁样行为。抑制前额叶皮质小胶质细胞激活和炎性因子的表达可能是其潜在的抗抑郁作用机制。

Objective:To investigate therapeutic effects of deep brain magnetic stimulation(DMS)on depressive-like behavior in a post-stroke depression(PSD)rat model and its potential mechanisms.Methods:Total 42 adult male SD rats were screened using sucrose preference test and open field test.They were randomly divided into sham surgery group(Sham group,n=6),stroke group(Stroke group,n=12),PSD group(n=12),and(PSD+DMS)group(n=12).Cerebral ischemia models were established induced by bilateral common carotid artery occlusion and reperfusion in groups stroke,PSD and(PSD+DMS).The common carotid artery of sham group was only separated without ligation.Groups PSD and(PSD+DMS)accepted chronic mild stress for 3 weeks,while(PSD+DMS)group rats accepted 40 Hz deep brain magnetic stimulation for 40 minutes per day for 2 weeks.The open field test was used to evaluate locomotor activity and anxiety-like behavior,while the sucrose preference test assessed anhedonia-like behavior.Immunofluorescence staining was performed to measure the expression level of Iba-1,a marker of glial cell activation,in the frontal lobe.Protein immunoblotting technique was used to detect the expression of CD11b,a marker of glial cell activation,as well as inflammatory cytokines IL-1βand TNF-αin the frontal lobe.Results:Treatment with DMS significantly improved depressive-like behavior in the(PSD+DMS)group compared to the PSD group.Glial cell activation and protein expression of inflammatory cytokines IL-1βand TNF-αwere increased in the frontal lobe of the stroke group.In the PSD group,further increase in glial cell activation and protein expression of IL-1βand TNF-αwas observed.However,in the(PSD+DMS)group,glial cell activation was reduced,and protein expression of IL-1βand TNF-αwas decreased.Conclusion:DMS treatment effectively improves depressive-like behavior in PSD rats.Inhibition of glial cell activation and expression of inflammatory cytokines in the frontal cortex may be potential mechanisms underlying its antidepressant effects.