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1.
目的::比较黑质致密部(SNc)损毁和内侧前脑束(MFB)损毁2种方法制备的帕金森病(PD)大鼠模型对纹状体中多巴胺(DA)递质含量的影响。方法:将大鼠随机分为假手术组(n=12)、SNc 损毁组(n=15)和 MFB 损毁组(n=14)。采用高效液相色谱-电化学检测法,观察3组大鼠损毁侧纹状体中 DA的含量。结果:与假手术组相比较,SNc 损毁组(P <0.001)和 MFB 损毁组(P <0.001)大鼠纹状体中 DA含量均显著降低,与 SNc 损毁组相比较,MFB 损毁组大鼠纹状体中 DA 含量下降更为显著(P =0.005)。结论:MFB 损毁制备的 PD 大鼠模型对 DA 能神经元的损伤范围较 SNc 损毁有所扩大,为不同研究选择制备模型的方法提供一定的理论依据。  相似文献   
2.
Glial cells have a major role in protecting neurons against various forms of stress. Especially, astrocytes mediate the bulk of glutamate clearance in the brain via specific membrane transporters (GLAST and GLT1), thereby preventing the occurrence of excitotoxic events. Although glutamate-mediated mechanisms are thought to contribute to nigral dopaminergic neuron degeneration in Parkinson's disease, detailed information on the organization of glia in the substantia nigra is still lacking. The present study was performed to provide quantitative information on the organization of astroglia and on the relationships between astrocytes and excitatory synapses in the rat substantia nigra. Using immunolabeling of GLT1 and confocal imaging, we found that the substantia nigra was filled with a dense meshwork of immunoreactive astrocyte processes. Stereological analysis performed on electron microscope images revealed that the density of immunoreactive astrocyte plasma membranes was substantial, close to 1 μm2/μm3, in the substantia nigra neuropil, both in the pars compacta and the pars reticulata. Excitatory synapses had on average two thirds of their perimeters free from glia, a disposition that may favor transmitter spillover. The density of glutamatergic synapses, as quantified on confocal images by the simultaneous detection of bassoon and of vesicular glutamate transporter 1 or 2, was very low (0.01 and 0.025 per μm3 in the reticulata and compacta subdivisions, respectively). Thus the ratio of GLT1-expressing glial membrane surface to glutamatergic synapses was very high (40–100 μm2), suggesting an efficient regulation of extracellular glutamate concentrations.  相似文献   
3.
IntroductionTo investigate whether neurodegeneration underlying Parkinson's disease (PD) accounts for a substantial proportion of cases of minimal parkinsonism in the elderly.MethodsWe recruited 48 consecutive subjects with minimal parkinsonism who visited the clinic with cognitive complaints. All subjects did not show findings compatible with PD on 18F-FP-CIT PET scans, and had no evidence of other neurodegenerative disorders. Striatal dopamine transporter (DAT) availability was quantified, and mean diffusivity (MD) values in the pons were calculated to characterize structural damage using diffusion tensor imaging. Additionally, 35 patients with PD and 21 healthy controls were included as reference groups.ResultsIndividuals with minimal parkinsonism (mean age, 73.23 ± 7.03 years) exhibited mild decrease in DAT availability in the posterior putamen, which was at a level between that of healthy controls and patients with PD. DAT availability in the caudate and anterior putamen was also mildly decreased in the minimal parkinsonism group. Individuals with minimal parkinsonism also tended to have higher MD values in the pons compared to healthy controls.ConclusionsOur results suggest that a substantial proportion of minimal parkinsonism is associated with nigrostriatal dopamine depletion and pontine structural damage, which may be related to the disease process of prodromal PD.  相似文献   
4.
Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.  相似文献   
5.
BackgroundTranscranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.MethodsA total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.ResultsTwo hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.ConclusionsThis is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.  相似文献   
6.
ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm2) was higher compared to iRBD (0.07 ± 0.07 cm2; p < 0.0001) and controls (0.05 ± 0.03 cm2; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.  相似文献   
7.
《Revue neurologique》2021,177(10):1214-1220
Two students of Jean-Martin Charcot, Paul Blocq and Georges Marinesco, presented a case of hemi-parkinsonism to the Société de Biologie on 27 May 1893. A tuberculoma was found at post-mortem in the cerebral peduncle contralateral to the side of the body affected by Parkinson's disease. A year later, in one of his lessons, Édouard Brissaud suggested that damage to the substantia nigra caused by the granuloma might have been responsible for the physical signs. This article provides brief biographical accounts of both Blocq and Marinesco and a detailed review of their seminal paper before going on to discuss how the substantia nigra was eventually established as the most consistent pathological substrate for Parkinson's disease and its role in the dopamine miracle which led to striatal dopamine replacement therapy in 1967.  相似文献   
8.
目的探讨磁共振神经突方向离散度与密度成像(NODDI)对帕金森病患者的临床应用价值。方法收集我院41例帕金森病(PD)患者,以22例年龄和性别匹配的正常志愿者作为对照组,行磁共振平扫和NODDI成像,量化分析PD患者黑质致密部(SNpc)及壳核的变化,在组间比较黑质致密部及壳核的细胞内体积分数(Vic)、方向分散指数(OD)和各向同性体积分数(Viso)。多变量逻辑回归分析确定PD的独立预测因子。结果PD患者SNpc及壳核中的Vic、OD明显低于健康对照组(P<0.05),多因素Logistic分析显示,帕金森病患者SNpc及壳核中的Vic值的变化与PD的相关性具有统计学意义(P<0.05),SNpc及壳核中的Vic值是PD的独立预测因子。在ROC分析中,患者对侧SNpc及对侧壳核中的Vic值显示出最佳的诊断性能。结论NODDI可以反映PD患者大脑微观结构的变化,其参数值可以作为PD患者的评估指标。  相似文献   
9.
ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.  相似文献   
10.
Parkinson’s disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of α‐synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as α-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management.  相似文献   
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