Objective To evaluate the ratio of hemi-Parkinsonism model induced by MPTP and compare with image and pathobiology. Methods After injecting MPTP in right side internal carotid artery, the ability to move was quantified by using a pedometer. The apomorphine evoked rotation was also tested. The metabolism of glucose within the monkey brain was measured by positron emission tomography (PET) using 18F-FDG, and the metabolism of dopamine was also measured by single photon emission computerized tomography (SPECT) using 99Tcm-TRODAT-1. Results Seven days after the injection of MPTP in right side internal carotid artery, the monkeys presented the Parkinson's disease symptoms and left-twirling. Examination of PET and SPECT showed that the radioactivity was much less in right midbrain and striatum than that in the contralateral side, there was significant difference between the pre- and post-operation groups or in right and left groups. Tyrosine hydroxylase positive neurons in the substainial nigra were obviously reduced. Conclusion The establishment of hemi-Parkinsonism model of rhesus induced by MPTP in right side internal carotid artery is a safe and simple way, and it is ideal for the study of Parkinson's disease.

目的研制一种动物专用立体定向仪进行动物实验研究.方法将其用于6只帕金森病猴手术,该立体定向仪与临床使用的立体定向仪运用原理相同,定位和手术步骤相似.结果 30d后动物自发旋转现象消失,无肌力减退及并发症发生.结论该动物专用立体定向仪安装、操作简单,动物固定可靠,定向准确.

Objective To observe the transfection ability to neuron and the therapy effect of adeno-associated virus vector (AAV) mediated intracerebal expressing of human tyrosine hydroxylase (TH) in the Rhesus monkey of Parkinson disease with CT guiding. Methods Six Rhesus monkeys were induced into hemi-parkinsonism models by infusion of MPTP into right internal carotid artery. Under the guidance of CT and stereotactic apparatus, the recombinant adeno-associated virus vectors-human tyrosine hydroxylase were injected into the right caudate nucleus of 5 PD monkeys. The motor ability of the PD model was evaluated for 6 months after implantation. The content of DA, DOPAC, and HVA in the caudate nucleus was assayed with HPLC, and the expression of the tyrosine hydroxylase gene was detected with immunohistochemistry and RT-PCR. Results The method of stereotactic puncture guided with CT had the features of real-time operating, fine location, and mini-trauma. The motor ability of all five models was all ameliorated after stereotactical injection of AAV-hTH vectors from two weeks up to six months. One PD monkey did not show any twist in response to apomorphine test. The frequency of twirl in the other 4 PD monkeys in response to apomorphine test was decreased by 42%-70% compared with that preoperatively. The contents of DA and DA metabolites in the lesion caudate nucleus were increased. Many TH positive cells in the implantation sites of caudate nucleus were shown by immunohistochemistry, which was different from the contralateral caudate nucleus. TH-mRNA was found in the treated side of caudate nucleus with RT-PCR, but no positive detection in the untreated side of caudate nucleus or in other sites in the brain. The negative results of RT-PCR were also shown in samples of the heart, liver, kidney tissue, or right side caudate nucleus of the uninjected monkey. Conclusion Under the guidance of CT and stereotactic apparatus, the AAV-hTH vector can be injected accurately into the lesioned caudate nucleus of PD Rhesus monkey model. That can effectually make the neuron express the features of TH gene in definite place. This therapeutic method can increase the caudate nucleus DA content and ameliorate the motor ability of PD model. The result suggests the gene therapy with AAV-hTH is a potentially valuable and safety therapeutic method for the primate model of Parkinsonism, and also provides some reference data of experiment for the clinical trial gene therapy in PD.

Objective To study the imaging appearance of experimental Parkinson′s disease (PD) and to evaluate the different medical imaging exams on PD. Methods CT, MRI, SPECT (dopamine transporter imaging and regional cerebral blood flow imaging, DAT imaging and rCBF imaging), and PET(glucose metabolism imaging) were performed on 8 monkeys before and after the infusion of MPTP into unilateral internal carotid artery to develop hemi-Parkinsonism models. Results Hemi-Parkinsonism models were successfully induced on all 8 monkeys. On DAT imaging, the uptake values of the lesioned striatums decreased obviously after the MPTP treatment and were lower than that of the contralateral ones. The glucose metabolic rates of the lesioned striatums and thalamus in PD models were lower, compared to that of the healthy monkeys and that of the contralateral sides of themselves. Neither DAT nor glucose metabolism abnormalities was found on both the contralateral sides of the healthy and PD monkeys. On MRI images before MPTP treatment, only 4 of 8 PD models showed hypointense in bilateral globus pallidus. No abnormal MRI findings occurred in the first 2 months after injection of MPTP. At the third month, hypointense appeared in globus pallidus of three monkeys. Enlarged hyposignal region in globus pallidus were found in three models. Of the above 6 monkeys, two appeared hypointense in putamina. Substantia nigra demonstrated no abnormalities before and after MPTP treatment. All rCBF and CT images were normal. Conclusion The decreased density of DAT and decreased glucose metabolism on experimental PD can be showed early by DAT imaing and glucose metabolism imaging. MRI can show abnormal signal in the basal ganglia of PD but it is later than DAT and glucose metabolism imaging. CT and rCBF find no abnormality on PD.