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The Influence Of The Cognition And Memory Ability After Stimulation By Subthalamic Nucleus-deep Brain Stimulation In Rats With Parkinson's Disease

Posted on:2018-11-23Degree:MasterType:Thesis
Country:ChinaCandidate:H LiFull Text:PDF
GTID:2334330536974366Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:Studies have shown that PD patients not only have dysmotility,but also with the decline in cognitive function,such as free memory,working memory and strategic memory,this decline even in the early PD patients appeared [1].It make seriously affect the quality of patients' life.Deep brain stimulation(DBS)has become a treatment of Parkinson's disease and other sports disorders surgical methods [2].But the previous researchers will focus on DBS on the role of dyskinesia,less concerned about the impact of cognitive memory.In this study,PD rats were prepared by 6-OHDA nucleus injection.Morris water maze was used in the treatment of STN-DBS.After treatment with DBS,Parkinson rat cognitive and memory whether there are changed,and then by immunohistochemical detection of hippocampus dopamine D1 receptor whether there is a change.Methods:In this study,PD rat model was established by two-point injection of 6-OHDA in rat unilateral midbrain substantia nigra(SNc)and midbrain ventral tegmental area(VTA),and apomorphine induced rotation identification Whether the model was successful.PD model was established after the tentacles forelimb reflex test to identify the degree of motor injury in PD rats.PD rats were divided into PD group,sham stimulation group and stimulation group according to random number table method.Fifteen rats were enrolled from the 30 PD model rats implanted with electrodes in a completely random number table.Daily fixed time to give continuous pulse stimulation,pulse 0.06 ms,stimulus output frequency of130 Hz,stimulus output intensity of 1.5v,stimulus duration of 30 mins,a total of 8d.For the sham stimulation group,the remaining rats in the stimulation group were excluded from the 30 PD model rats implanted with electrodes.The sham-stimulated group of electrodes were implanted with surgical methods and animal feeding conditions with the stimulation group,the electrodes were connected to the electrophysiological stimulator and stimulated isolators,but were not energized.(APO)rotation behavior test and Morris water maze were measured before and after stimulation.Histologically examined paraffin-embedded sections were cut to STN to see if the position of the stimulus electrode was accurate.Dipamine D1 receptor staining was performed by anti-tyrosine hydroxylase(TH)and hippocampus using immunohistochemical two-step method.To explore whether long-term high-frequency electrical stimulation has a protective effect on cognitive memory of PD rats.Results:1.Nissl staining results showed that the 6-OHDA PD model was injected into the target nucleus,SNc and VTA.Potassium ferrocyanide perfusion results showed that the el ectrode was accurat ely implant ed int o th e brai n STN posi ti on.2.The results of the first part showed that the successful hemolytic PD model was prepared by injecting 6-OHDA into the healthy male SD rats SNC and VTA and induced by apomorphine(APO)induction.The mice showed positive reflex.This is the PD rats brain injury contralateral limb movement disorders to make accurate identification.And then through the Morris water maze to do cognitive memory experiments,visible positioning navigation experiments: after 4 days of training: 1)Compared with the normal group,PD group can not be through the training stage,and swimming trajectory fixed in the various quadrants.(P<0.01);2)The average swimming speed in the normal group was significantly lower than that in the PD group(P=0.009),and the difference was statistically significant(P<0.01)Group;3)the swimming distance was significantly increased(P<0.01).Space exploration experiments: 1)the normal group of rats using spatial clues,trajectories are located in the platform quadrant,Parkinson rats swimming around the pool,trajectories distributed in the various quadrants.2)The percentage of platform quadrant movement time and the percentage of platform distance in the normal group were more than those in the PD group(P <0.05).3.The second part of the first part of the basis of the first 8 days after the start STN-DBS stimulation experiment.Fifteen rats were enrolled from the 30 PD model rats implanted with electrodes in a completely random number table.As results,There was no significant difference in the number of revolutions before and after stimulation,and there was no significant difference between the stimulation group and the PD group before stimulation.When the stimulation group was stimulated,the number of revolutions decreased significantly(P<0.01),and the number of revolutions was increased at 2 min after stimulation,but still significantly lower than before stimulation.Morris water maze test results positioning navigation experiments: after 4 days of training: 1),stimulation of rats after a period of training and guidance,and ultimately some rats can find and climb the platform.(P<0.01),while the mean escape latency was significantly lower in the normal group than in the PD group(P =0.009)and the fake stimulation group(p = 0.006),respectively,and the difference was statistically significant The remaining three groups.There was no significant difference between the two groups(P> 0.05);2)The average swimming speed of the stimulated group was significantly lower than that of the PD group(P=0.002)and the sham stimulation group(P=0.002)Was significantly higher than that in the normal control group(P = 0.001).There was no significant difference between PD group and sham stimulation group(P>0.05);3)PD group(P=0.020)and fake stimulation group(P=0.001)were significantly more than swimming group,the difference was statistically significant.Space exploration experiments: 1)the normal group of rats using spatial clues,trajectories are located in the platform quadrant,Parkinson rats and fake stimulation of rats around the pool wall swimming,trajectories distributed in the various quadrants.(P=0.003)and sham-stimulated group(P=0.022)increased,and the number of patients in the stimulation group was higher than that in the PD group and the group There was no significant difference between group and sham stimulation group(P=0.510).The results of immunohistochemistry showed that the levels of tyrosine hydroxylase(TH)and dopamine D1 receptor in the hippocampus were significantly lower than those in the normal control group.There was no statistically significant difference between the TH groups in the other three groups except the normal group(P>0.05).The number of dopamine D1 receptor cells in the stimulated group was significantly higher than that in the PD group and the sham stimulation group(P<0.05),which was statistically significant.Conclusion:PD rats have cognitive and memory problems,and there are significant differences with normal rats.After STN-DBS treatment,behavioral examination has a significant effect.MWM experiment has proved that cognitive ability has been improved.Dopamine receptors that affect cognitive ability have a certain protective effect,may be due to DBS to promote the release of a neuroprotective factor,delayed the development of the disease.
Keywords/Search Tags:Parkinson's disease, Learn and Memory, STN-DBS, Rat, Dopaminergic D1cell
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