| Parkinson's disease (PD) is a progressive neurodegenerative disorder. The pathologic hallmark of the disease is the degeneration of dopaminergic neurons of the substantia nigra pars compacta, which leads to severe dopaminergic denervation of the corpus striatum. Deep brain stimulation of subthalamic sucleus (STN DBS) can improve most symptoms of mid or late stage PD patients with less complication, long term symptom regression, and decrease of antiparkinsonian drug dose. But many issues related to STN DBS remained to be answered, including basic questions as mechanism of action, long-term outcome and clinical indications.The pathologic hallmark of PD is the degeneration of melanine-containing, dopaminergic neurons of the substantia nigra pars compacta, the dopaminergic deficit of the nigrostriatal system is accompanied by functional modifications of the other basal ganglia nuclei. Dopamine (DA) plays an important role in progession and treatment of PD. It is reported that striatal dopaminergic metabolism is increased by HFS of STN in 6-hydroxydopamine lesioned rats. But some clinical researchs indicated that STN DBS does not increase the striatal dopamine concentration in parkinsonian humans. The HFS which previous animal experimental studies used were short-time stimulation, and the PD animal model of rats induced by 6-hydroxy-dopamine (6-OHDA) is different markedly from PD of humans. There are many limits in clinical researchs. So we use nonhuman primate PD models induced by MPTP, which is most similar to idiopathic PD of human. And hemiparkinsonian monkeys were treated by long-term chronic high frequency stimulation of STN. We observed change of striatal dopamine function by single photon emission computed tomography (SPECT), positron emission tomography (PET), MRI and pathophysiology. We analyzed the potential mechanism of STN DBS by experimental data, which may lead to understanding of STN DBS as well as to new effective treatment modality for delaying or stoping the procession of PD.Partâ… : Hemiparkinsonian monkey models induced by MPTP Objective: Hemiparkinsonian monkey models can be induced by unilateral internal carotid artery infusion of 1-methy-4-phenyl-1,2,3,6-tetrahydropy-rindine (MPTP) with two different methods ,endovascular and direct surgical approach, are similar to that of Parkinsonian humans.The objective of this part is to provide PD monkey models for STN DBS experiment, simultaneously, to compare two kinds of methods. Methods: Two healthy senior rhesus monkeys with wights ranging form 5~7kg were used in this study, all more than 10-year-old. There are two methods to establish monkey models of hemiparkinsonism with MPTP. Endovascular approach: Two monkeys, after general anesthesia, were punctured of femoral artery. The internal carotid artery was catherized and MPTP saline (0.2mg/ml) was injected slowly under fluoroscopy.Direct surgical approach: Two monkeys were included in this group. After general anesthesia, the right common carotid artery and bifurcation was exposed by blunt dissection. MPTP saline (0.2mg/ml) was injected into the right common carotid artery slowly after cliping of the external carotid artery.All monkeys were evaluated after surgery according to a disability rating scale. The apomorphine evoked rotation was also tested. MRI verified the changes of substantia nigra and striatum of hemiparkinsonian monkeys were verified with MRI, and dopamine transporter (DAT) and D2 receptor (D2R) of striatum were measured using SPECT. The metabolism of dopamine of the lesioned side was compared with that of the normal side, which verified the impairment of nigrostriatal dopaminergic system induced by MPTP. After 6 months, both sides of striatum and substantia nigra of the monkey brain were cut into serial sections, and tyroxine hydroxylase (TH) immunohistochemistry study was performed. DA and its metabolites in cerebrospinal fluid (CSF) were tested with high performance liquid chromatography and electrochemical detection (HPLC-ECD) pre- and post-infu...
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