| Background and Purpose:Parkinson's disease(PD) as a common neurodegenerative disease,has an extreme threat on human health,especially on the older man.Bradykinesia,tremor,rigidity and gait dysfunction are major symptoms about advanced PD.Although levodopa(L-DOPA) is the standard medicine treatment,medicine induced syptom fluctuation and medicine related side effect will present.Deep brain stimulation(DBS) as a therapic option for advanced PD patients is used in motor disease as PD,essential tremor,dysmyotonia and so on, widely accepted by Western people.Safety(no permanent damage to brain tissue),flexibility(adjustable stimulation parameters) and reversibility(ability to stop when more advanced treatment becomes available) are three important advantages of DBS over surgical ablation treatments or medicine therapy.Nevertheless STN-DBS on PD can achieve well effective,the mechanism is unclear.Through the study of the mechanism of DBS,people can not only consummate the therapy and make it precisely in patients,but also provide the scientific evidence of it and expand its indication.There is no distinctive discrepancy of brain structure in morphology between normal people and PD patients.Positron emission tomography(PET) is an advanced medicine imageology tool,could make early diagnosis from molecular nuclear medicine level by detect body metabolism. Small animal PET(microPET) with a higher resolution when compared with popular PET,can detect metabolism of smaller brain structures. Our research use 18F-fluoro-2-deoxyglucose (18F-FDG) and 3-N-[11C] methylspiperone (11C-NMSP) microPET to assess regional cerebral glucose metabolism and expression of dopamine receptor type 2(DRD2) in a rat model of PD pre-and after STN-DBS.Methods:Rats were randomly assigned to two group:rats to make PD models was managed by infusion of 4μL 6-OHDA(2μg/μL,containing 2%ascorbic acid)in right nigra compacta(SNc) and ventral tegmental area(VTA) respectively;sham-operated by infusion 4μL sterile(containing 2%ascorbic acid) in SNc and VTA.Using apomorphine to assess model success or not two weeks later.Select success PD models(n=12) and sham-operated rats(n=10) to accept 18F-FDG and 11C-NMSP microPET scan respectively.Implant the cannula in the right STN after microPET scan.Two weeks later all rats were received unilateral STN-DBS.Rats were undertaken 18F-FDG microPET scan on pre-stimulation,3 days and 2 weeks later after stimulation,11C-NMSP microPET scan was commit 5 days after stimulation.The 18F-FDG microPET and MRI images were co-registered using ASIPro VM software.In order to observe the glucose metabolism modification in pre-and after stimulation,region of interest(ROI) was draw on the striatum,the sensorimotor cortex,the hippocampus,the thalamus,the pons and the cerebellum.In order to compare the expression of DRD2 in the striatum pre-stimulation with post-stimulation,we draw ROI on the striatum of 11C-NMSP microPET images.Then we conducted the immunohistochemistry to testify the success PD model. We use Nissl to make sure the spot of stimulator tips location after PET scan,only adopt the data of the rats which stimulator tips on the STN. Results:APO induced rotational reaction on PD model,rotations more than 7r/min were success PD model,no reaction was found at the sham-operated rats. Immunohistochemistry results show that TH positive neurons were decrease markedly in the right SNc,expression of DRD2 positivie neurons was significant increased in the right striatum.There was no obvious change in the left side(intact side). Nissl staining shows that stimulator tips were on STN.In PD models, when compared to intact side,glucose metabolism had a significant decrease in right striatum,hippocampus and sensorimotor cortex,but there was no obvious discrepancy in the thalamus,pons and cerebrellum.Glucose metabolism in the striatum,the hippocampus and the sensorimotor cortex was significant lower than the control group.After unilateral STN-DBS therapy,glucose metabolism in the right hippocampus,the sensorimotor cortex and the thalamus of PD model was increased significantly, in the cerebellum which was decreased significantly in cerebellum.These effects maintained to two weeks later,but an obvious decrease tendency was observed in the hippocampus and the thalamus.In PD rats,the expression of DRD2 in the right striatum was significant higher than the intact side,also significant higher than control group,but there was no incredible difference when compared pre-stimulation with post-stimulation.Conclusion:1.18F-FDG and 11C-NMSP microPET could effectively assess the regional cerebral glucose metabolism and expression of DRD2 in PD, which might be used as effective molecular imaging tools for early diagnosis of PD.2.The therapeutic effects of unilateral STN-DBS maybe from modulates the glucose metabolism of hippocampus,sensorimotor cortex and thalamus in hemi-parkinson's rats.
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