Experimental Study On Mechanisms Of Treatment Of Parkinson's Disease With Lesion Of Ventral Pallidum In Rats

Objective: To oberserve the effect of Parkinson's disease (PD) rats by microelectrodelesion neucli of ventral pallidum(VP),detect the change of neural transmitter andmorphology in the brain, to explore the mechanism of cell knife therapy PD.Methods: A total of 120 adult Sprague-Dawlay(SD), weighting 250-300g ,byinjecting 6-OHDA into left substantia nigra pars compact(SNc) and ventral tegmentalarea(VTA) of rat and inducing with apomorphine, we escablished Parkinson'sDisease(PD) modle. After lesioning procedure was determined by measuring thenumber of full turns over 30 min following intraperitoneal injection ofapomorphine(APO). Only those had mean net rotation of seven turns/min wereused.Then those rats were received surgery with microelectrode lesioning, and therotational behavior of rats were observed by APO induced. Those rats were sacrificedat 1,2,4 and 8 weeks after the surgery procedure, and neural necrosis and apoptosis wasoberserved with Hematoxylin and eosin(HE) staining and Caspase-3immunohistochemistry staining. The change of TH positive cell and NOS positive cellwere observed with TH immunohistochemistry and NADPH-d histochemistrystaining.Then content of neuro transmitter about amino acid and monamine wasdetected with High Performance Liquid Chromatography(HLPC).Results: 1.After VP lesion, compared with the number of rotation of lesion rats wassignificantly decreased(P<0.05).2. HE staining show:area of VP zone neural necrosiswas observed in central area of VP lesion zone.There was some tissue falled in the VPlesion region, little eosinophilic cytoplasm no cell structure, histological signs of aninflammatory response were present,with perivascular coffing and infiltration of cellsaround VP lesion region.3.Compared with normal rats, NADPH-d positive cells in thestriatum increased(P<0.05), and those positive cells in the ipsilateral striatum of VPlesion group were also increased. Compared with PD and sham group,there wasmarkedly difference(P<0.05).4.Results of TH immunohistochemistry staining revealed Ⅲ英文摘要TH positive cells in SNC of PD were significantly lower than normalrats(P<0.05).There was no differdnce among VP lesion PD rats and shamgroups(P<0.05).5.there were many Caspase-3 positive cells in the SNc of PD rats,andno change of number of Caspase-3 positive cells in VP lesion and sham surgry groupswas ovserved(P>0.05),but around VP lesion region,Caspase-3 positive cells werestrikingly increased,compared with PD group and sham groups(P<0.05).6.Result ofHPLC indicated: ① Content of DA was significantly less than normalgroup(P<0.01).After lesion of VP content of DA was also strikinglydecreased,compared with PD rats and sham groups.②Content of Glu was lower thannormal rats(P<0.05).After VP lesion ,content of Glu was remarkablely increased,andreached the peak at 2 weeks, then subsiding by 14 days but higer than control groups.③Content of GABA in PD rats was less than that of normal rats(P<0.05).After VPlesion, content of GABA was no change at one week, and obvious increased at 2weeks(P<0.05),then decreased gradually but much high than PD group in 2 months.Conclusions: 1.The rotational behavior of PD rats was significantly improved by VPlesion.2.Production of DA was remarkablely influenced by VP lesion.Contents ofamino acid reach the Peak at 2 weeks after VP lesion,then decrease gradually.3.VPlesion can obviously improved symptom of PD,it maybe result from lesion of VPinhibited abnormal discharge,and the increased NO content in the striatum canlonger reinforce the injury to VP,and the toxicity of exciting amino acid,and theapoptosis in lesion region.