Efficacy And Mechanism Of Repetitive Transcranial Magnetic Stimulation (TMS) On Depression-like Behavior In Mice After Ischemic Stroke

Objective:In this study,bilateral common carotid artery ligation was used to establish a mouse model of post-stroke depression(PSD),and Fluoxetine(Flu)was administered with repetitive transcranial magnetic stimulation(r TMS)alone and both together,depression in mice after treatment by observing the behavior of the change,to explore the therapeutic effect of r TMS on poststroke depression in mice and the possible mechanism of r TMStreatment,by observing the changes of depression-like behavior in treated mice,the therapeutic effect of r TMS on post-stroke depression mice and the possible mechanism of r TMS treatment were investigated.Methods:BALB/c male mice aged 6-8 weeks(weight 25-30g)were reared in a quiet environment with a 12-12 hour day/night cycle,free access to food and water,and adapted to the new environment for 1 week before the experiment.With Bilateral common carotid arteries ligation method(as common carotid artery occlusion,BCCAO)Model of ischemia in mice,according to the different way of intervention to produce five groups:control + salinegroup(sham),bilateral common carotid arteries ligation + saline group(Model),bilateral common carotid artery ligation +fluoxetine group(Flu),bilateral common carotid arteries ligation + r TMSgroup(r TMS),bilateral common carotid arteries ligation +Flu + r TMSgroup(Flu + r TMS).After 4 weeks of intervention,the improvement of depression-like behavior in mice was detected by behavioral experiments.Western blot was used to conduct quantitative analysis of BDNF in thehippocampus of mice.The behavioral experiment and organization based was conducted 24 hours after the last intervention.The stimulation parameters of r TMS were high frequency 10 Hz,and the mice in each group were bound to facilitate the treatment of r TMS.Fluoxetine 10mg/kg,daily intraperitoneal injection,behavioral experiments included:tail suspension test,open field experiment,high cross maze experiment.Results:(1)In the tail suspension experiment,compared with Sham group,the immobility time of Model group was significantly prolonged(P<0.05),compared with the Model group,the immobility time of the Flu group and the Flu+r TMS group decreased(P<0.05),there was no significant difference between the treatment group and Sham group(P>0.05).(2)In the openfieldexperiment,compared with the Sham group,the total movement distance and the movement distance in the external area of the Model group were significantly reduced(P<0.05),compared with the Model group,the total distance of movement and the distance of movement in external areas of the r TMS group and the Flu+r TMS group significantly increased(P<0.05),there was no significant difference between the treatment group and Sham group(P>0.05).(3)In the high cross maze experiment,compared with Sham group,the number and time of entry into open arms in the Model group were significantly reduced(P<0.05),compared with the Model group,the number and time of enter into open arms in the Flu group and the Flu+r TMS group significantly increased(P<0.05),there was no significant difference between the treatment group and Sham group(P>0.05).(4)BDNF expression levels:compared with Sham group,the expression levels of BDNF in the hippocampus of the Model group decreased significantly(P<0.05),compared with the Model group,the expression levels of BDNF in the hippocampus of the Flu group and the Flu+r TMS group increased(P<0.05),there was no significant difference between the treatment group and Sham group(P>0.05).Conclusion:1?rTMS treatment can improve the depression-anxiety-like behavior of mice induced by ischemic stroke.2?After ischemic stroke,the expression of BDNF in the hippocampal region of mice decreased,but after r TMS and drug treatment,the expression of BDNF in the hippocampal region of mice increased.3?The mechanism of rTMS therapy to improve the depression-anxiety-like behavior of mice after ischemic stroke may be related to the stimulation of r TMS to up-regulate the expression of BDNF protein in the hippocampus,regulate synaptic plasticity,and promote the proliferation of hippocampal cells.