The Experimental And Clinical Study On Neuron Functional Imaging For Parkinson's Disease

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder among middle age and old-age persons. PD's cardinal manifestations are tremor, rigidity, bradykinesia and postural instability et al. The episode rate increased year by year as the course of population aging. According to literature's report, about 1% population above 55 years old were patients with PD in our country. Motor disability caused by PD burden on families and society. There are two topics in clinical practices: how to diagnosis PD early and how to neuroprotect PD. At present, the diagnosis of PD still depends on clinical criteria. Recent studies showed that an unexpectedly high rate of misdiagnosis occurred if the diagnosis was based on only the clinical diagnostic criteria only. In addition, motor disturbances began only after a loss of approximately 70%-80% of striatal dopamine, resulting in a long "latent" stage preceding the development of clinical manifestations. There is no objective technique in early diagnosis of PD. PET and SPECT have enabled noninvasive, in vivo visualization of the progression of striatal neuronal function including dopamine transporter (DAT) and dopamine receptor (DR) in PD. 99Tcm-TRODAT-1 is a novel DAT SPECT agent. 11C-raclopride is a commonly used D2R PET agent. At the basis of success establishment of Hemi-parkinsonism monkeys, we investigated the functions of DAT and D2R in subclinical and clinical PD monkeys using above two agents. To explore the values of 99Tcm-TRODAT-1 SPECT brain imaging and 11C-raclopride PET brain imaging in the early diagnosis of PD, especially in the diagnosis of subclinical PD. In clinical research part, we investigated the clinical values of 99Tcm-TRODAT-1 DAT SPECT imaging in early diagnosis of patientswith PD. We also evaluated the values of 99Tcm-TRODAT-1 DAT SPECT imaging for assessing the degrees about the severity of patients with PD. To investigate the relationship of striatal 99Tcm-TRODAT-1 specific uptake values (SUVs) and motor's severity in patients with PD. Selegiline is a common monoamine oxidase-B inhibitor. According to literatures, selegiline may be having neuroprotective effects in the progression of PD. At the basis of establishment of mice with MPTP-induced parkinsonism, we investigated the selegiline's neuroprotective effects on substantia nigra using flow cytometry (FCM), thyrosine hydroxylase (TH) immunohistochemistry and transmission electorn microscope (TEM). We also investigated selegiline's neuroprotective effects on striatal DAT using 99Tcm-TRODAT-1 agent. The thesis was composed of five parts: â… . The neuroprotective effects of selegiline on substantia nigra neurons of mice with MPTP-induced parkinsonism. â…¡. Study on the values of 99Tcm-TRODAT-1 DAT SPECT in diagnosis of subclinical PD monkey.â…¢.Study on the values of 11C-raclopride D2R PET in the diagnosis of subclinical and clinical PD monkey. â…£. Study on values of 99Tcm-TRODAT-1 DAT SPECT in the early diagnosis and assessing the severity of patients with PD.â…¤. Relationship of striatal 99Tcm-TRODAT-1 specific uptake and motor's severity in patients with Parkinson's disease.Part â… : The neuroprotective effects of selegiline on substantia nigra neurons of mice with MPTP-induced parkinsonism Objective: To investigate the neuroprotective effects of selegilne on substantia nigna neurons of PD mice. Methods: 24 male C57BL mice were divided into three groups randomly (each had 8 mice). Three groups of C57BL mice treated with selegiline plus MPTP, MPTP and normal saline, respectively, for 7 days before performing FCM, TEM and TH immunohistochemistry in substantia nigra. Mice of selegiline group were fed 10mg/Kg selegiline daily for 7 days, a half an hour prior to 30mg/Kg MPTP treatment. Mice with MPTP-induced parkinsonism were received intraperitoneal injection of 30mg/Kg MPTP once a day for 7 days. Mice ofcontrol group received normal saline intraperitoneally once a day for 7 days. Apoptosis rate, bcl-2 protein expression mean fluorescence intensity (MFI), bax...