The Effect Of Deep Brain Stimulation In The Internal Globus Pallidus On The Gait In "OFF Period" Of L-DOPA-induced Dyskinesia Rats

ObjectiveLevodopa-induced dyskinesia(LID)is one of the most severe complications in advanced Parkinson’s disease.It occurs in the late stage of patients taking levodopa for treatment.LID is a series of involuntary movements,just like chorea,and the symptoms disappear as the efficacy of levodopa go away.This makes levodopa therapy difficult to sustain.What’s more,the mechanism of LID is not fully understood.Clinically,deep brain stimulation in the internal globus pallidus(GPi-DBS)has shown significant effects to treat LID.Currently,much research focus on the period of LID,the period of involuntary movement after taking Levodopa.However,few research has been conducted on the gait of Parkinson’s disease after LID and on whether GPi-DBS can improve the gait.In our experiment,we established a rat model of dyskinesia in hemiparkinsonism,so as to study the change of gait in LID rats and to discuss whether GPi-DBS can improve the gait of rats after the onset of LID,as well as LID itself.Method34 SPF Sprague-Dawley male rats was used in this study.Each rat weights 280-300g.The animals were randomly divided into 4 groups:(1)Sham Group with saline injection,n=8.(2)Parkinson’s Disease(PD)Group,n=10.(3)Levodopa-induced dyskinesia(LID)Group,n=8.(4)Deep Brain Stimulation in the internal Globus Pallidus(GPi-DBS)Group,n=8.In order to model Parkinson’s disease,6-OHDA was injected to damage the substantia nigra pars compacta of the right-side brain in rats.Then L-DOPA was intraperitoneally injected for 21 days to model LID animals.During these days,rats was assessed according to AIMs.Electrode implantation was performed in LID rats.One week after the surgery,GPi-DBS was performed in rats except Sham-stimulation Group.Catwalk XT system was used to analyze the gait of rats in each group.The Stand,,Stride Length,Swing Speed,Print Area,Base Of Support and Terminal Dual Stance of each paws were recorded.In each group,3 rats were selected for TH staining and electrode localization.Excitatory postsynaptic currents(EPSCs)of other rats were detected by patch clamp technique.Results(1)AIMs scores:all scores of the rats in the LID group increased with the increase of medication days,and will reach the plateau on the 14th day.Compared with the CTR group,all scores of the LID group increased significantly on the 21st day.Compared with the LID group,the score of the DBS group showed a decreasing trend.(2)Catwalk analysis:compared with the PD group,the gait of the LID group were significantly deteriorated,while those of the GPi-DBS group were significantly improved.Among the four indexes of Stand,Swing Speed,BOS and Terminal Dual Stance,the value of the PD group was higher than that of the CTR group and lower than that of the LID group.The value of the DBS group was between that of the LID group and the CTR group.(3)Cortical M1 excitatory postsynaptic current:compared with the CTR group,the amplitude of EPSCs in the PD group and the LID group was significantly increased;compared with the LID group,the amplitude of EPSCs in the GPi-DBS group was significantly decreased.Conclusion(1)after long-term administration of levodopa,the gait of LID rats was significantly more severe than that of Parkinson rats,indicating that long-term administration of levodopa would reduce the therapeutic effect;(2)GPi-DBS can effectively alleviate the involuntary movement of LID rats.Meanwhile,it can improve the gait and posture of LID rats.(3)GPi-DBS may improve the gait and posture of off-set LID rats by regulating cortical excitability.