首页 | 官方网站   微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 125 毫秒
1.
Higher levels of proinflammatory cytokines are found in Parkinson's disease (PD) patient's brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of proinflammatory cytokines act on the endothelium of blood-brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this upregulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease, Br. J. Pharmacol. 50, 963-976; Kortekaas, R., Leenders, K.L., Van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176-179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha were significantly higher in PD patients than in HC subjects (p<0.001), as determined by RT-PCR and Elisa methods. Cyto/chemokine levels were significantly correlated with UPDRS III and H/Y stage (p<0.001). The Pearson's correlation coefficient (R) was also used to assess the strength of the relationship between NF-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD.  相似文献   

2.

Background

In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD.

Methods

We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed.

Results

RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1 = 0.644, p = 0.033 and rs2 = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels.

Conclusion

The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.  相似文献   

3.
Background – Interleukin (IL)‐12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL‐10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL‐10. There is little information about the involvement of IL‐12 or IL‐10 in the pathophysiology of Parkinson’s disease (PD). Objectives – The objective of our study was to assess the role of IL‐12 as a potential marker of immune reactions in patients with PD and to investigate whether IL‐10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD. Patients and methods – We measured using immunoassay serum IL‐12 and IL‐10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL‐12 and IL‐10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score. Results – The PD group presented with significantly increased IL‐10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL‐10 and IL‐12 levels was observed in patients with PD (RS = 0.7, P < 0.000001). Conclusions – Our findings suggest that IL‐10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL‐10 and the significant correlation between IL‐10 and IL‐12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.  相似文献   

4.
目的 探讨帕金森病(Parkinson’s disease,PD)患者血清微小RNA(miR)-128,miR-221的表达水平变化及其对疾病的辅助诊断价值。方法 选取2016年1月-2019年12月本院收治的PD患者210例作为PD组,均根据Hoehn-Yahr分级进行分组,4~5期的患者纳入到重度组(60例),2.5~3期的患者纳入到中度组(82例),1~2期患者纳入到轻度组(68例); 收集同期本院的体检志愿者60例作为对照组; 检测所有研究对象的血清miR-128,miR-221表达水平,收集患者的病程以及统一帕金森病评定量表(Unied parkinson disease rating scale,UPDRS)评分。结果 PD组血清miR-128水平低于对照组,血清miR-221水平高于对照组(P<0.05); 重度组血清miR-128水平低于中度组和轻度组,血清miR-221水平高于中度组和轻度组(P<0.05),中度组血清miR-128水平低于轻度组,血清miR-221水平高于轻度组(P<0.05); 经Pearson分析显示,PD患者血清miR-128水平与UPDRS II评分、UPDRS III评分、Hoehn-Yahr分级均呈负相关(-0.5<r<0,P<0.05),血清miR-221水平与UPDRS II评分、UPDRS III评分、Hoehn-Yahr分级均呈正相关(0<r<0.5,P<0.05); 受试者操作特征曲线(Receiver operating characteristic curves,ROC)分析显示,血清miR-128,miR-221对PD有较高的早期辅助诊断价值,其曲线下面积均大于0.7; 联合诊断的敏感度和约登指数均有所提升,联合诊断对PD的早期辅助诊断价值更高。结论 PD患者血清miR-128水平呈异常低表达、miR-221水平呈异常高表达,二者均与患者的病情严重程度存在一定的相关性,且对PD有较高的早期辅助诊断价值。  相似文献   

5.
目的 探讨帕金森病(Parkinson's disease,PD)患者脑脊液(CSF)生物标志物的水平变化及其临床意义。方法 选取本院2018年3月-2019年3月收治的70例PD患者,并根据改良PD综合评分量表(UPDRS量表)及Hoehn-Yahr评分标准将患者分为轻度组(n=38)、中度组(n=18)和重度组(n=14)。另选择同期于本院接受体检健康人员70例作为对照组,检测并比较4组研究对象CSF生物标志物蛋白α-突触核蛋白(α-syn)、磷酸化Tau蛋白(P-Tau)及总Tau蛋白(T-Tau),微小RNA133 b(miR-133b)及C反应蛋白(CRP)、白细胞介素-8(IL-8)水平。结果 各组性别、年龄比较无明显差异(P>0.05); 不同病情严重程度PD患者UPDRS评分比较有明显差异,且均显著高于对照组(P<0.05); PD患者轻度组、中度组及重度组H-Y评分比较有明显差异(P<0.05)。各组α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平比较有明显差异(P<0.05),且随着PD患者病情严重程度加重,α-syn水平显著降低,P-Tau、T-Tau、miR-133b、CRP及IL-8水平显著升高(P<0.05)。Pearson相关分析显示,α-syn与UPDRS评分呈显著正相关,P-Tau、T-Tau、miR-133b、CRP及IL-8与UPDRS呈显著负相关(P<0.05)。受试者工作曲线(ROC)显示α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平诊断PD的曲线下面积(AUC)分别为0.755、0.785、0.742、0.746、0.779、0.755,联合诊断的AUC为0.905。结论 脑脊液生物标志物的水平变化是PD发生与发展的重要参考指标,其对于PD的诊断和病情严重程度判断具有重要价值  相似文献   

6.
BackgroundRecently, increased serum insulin-like growth factor-1 (IGF-1) levels have been reported in patients with Parkinson's disease (PD) and multiple system atrophy (MSA).ObjectiveTo assess a correlation between the serum IGF-1 levels and clinical background factors in patients with PD and related disorders such as MSA and progressive supranuclear palsy (PSP).MethodsA total of 79 PD patients, 25 MSA patients, 16 PSP patients and 52 healthy controls were included in this study. The serum IGF-1 and growth hormone (GH) levels were measured in a fasting state. Unified PD Rating Scale (UPDRS) part III was used to evaluate motor function. Unified MSA Rating Scale (UMSARS) part II was also employed for the MSA patients.ResultsThe serum IGF-1 levels were significantly increased in the MSA patients compared with the PD patients and controls. No significant differences were observed in the serum GH levels among the patients and controls. The serum IGF-1 levels of PD patients with Hoehn and Yahr stage 2 were significantly higher than those of patients with Hoehn and Yahr stages 3–5. In patients with PD and PSP, the serum IGF-1 levels were negatively correlated with UPDRS part III. In contrast, patients with MSA showed a positive correlation of the serum IGF-1 levels with disease duration, UPDRS part III and UMSARS part II.ConclusionThe difference in the serum IGF-1 level and its correlation with clinical variables among these disorders may reflect different ongoing disease processes in each disorder.  相似文献   

7.
Background: Pathological accumulation of α‐synuclein, amyloid‐β42, and tau proteins in the brain is considered critical for development of various neurodegenerative diseases. Objectives: We investigated the association between CSF levels of these biomarkers, brain structural connectivity, and the UPDRS in PD. Methods: Diffusion tensor images and CSF biomarkers (α‐synuclein, amyloid‐β42, total tau, and phosphorylated tau181) from 132 drug‐naïve, nondemented PD patients and 61 healthy controls were obtained from the Parkinson's Progression Markers Initiative database. After network reconstruction of structural connectivity patterns, global interconnectivity measures (including global efficiency, clustering coefficient, and characteristic path length) and local efficiency were calculated. Network properties and CSF biomarkers were compared between PD patients and healthy controls. The association of CSF biomarkers with network properties and UPDRS‐III score was investigated. Results: Global measures (but not local efficiency) and CSF α‐synuclein were significantly lower in PD patients. Global efficiency and clustering coefficient correlated positively with α‐synuclein, Aβ42, and total tau CSF levels. Furthermore, these CSF biomarkers showed no significant association with the UPDRS‐III score. Conclusions: This study examined the association of CSF biomarkers that reflect the brain pathology, with structural brain connectivity and UPDRS‐III in PD. Our results revealed an association between the abnormal aggregation of α‐synuclein, Aβ42, and tau proteins and structural connectivity disruption in PD patients. In summary, a combination of structural imaging and measurement of CSF biomarkers provide a better understanding of the pathogenesis of PD. © 2018 International Parkinson and Movement Disorder Society  相似文献   

8.
BackgroundVariations of α-synuclein levels have been reported in serum and plasma in Parkinson's Disease (PD) Patients.MethodsSerum and plasma were obtained from PD patients without known mutations (GU-PD, n = 124)), carriers of the A53T/G209A point mutation in the α-synuclein gene (SNCA) (n = 29), and respective age-/sex-matched controls. Levels of total α-synuclein were assessed using an in-house ELISA assay.ResultsA statistically significant increase of α-synuclein levels was found in serum, but not plasma, from GU-PD patients compared to healthy controls. A statistically significant decrease of α-synuclein levels was found in serum and plasma from symptomatic A53T mutation carriers compared to healthy controls. Plasma α-synuclein levels were modestly negatively correlated with UPDRS part III score and disease duration in A53T-PD patients.ConclusionIncreased α-synuclein levels in serum of GU-PD patients suggest a systemic deregulation of α-synuclein homeostasis in PD. The opposite results in A53T-PD highlight the complexity of α-synuclein homeostatic regulation in PD, and suggest the possibility of reduced expression of the mutant allele.  相似文献   

9.
Interleukin-15 (IL-15) is a novel proinflammatory cytokine having similar biological activities to IL-2 which is implicated in the pathogenesis of multiple sclerosis. It is produced by activated blood monocytes, macrophages and glial cells. There is little information about the involvement of IL-15 in the development of multiple sclerosis (MS). The objective of our study was to measure IL-15 serum and cerebrospinal fluid (CSF) levels in MS patients and to correlate serum and CSF IL-15 concentrations with clinical parameters of the disease. CSF IL-15/Serum IL-15 ratio (c/s IL-15 ratio) was introduced to assess the origin of elevated IL-15 levels. MATERIALS AND METHODS: We measured serum and CSF IL-15 levels in 52 patients with MS and 36 age and gender matched patients with inflammatory (IND) and non-inflammatory neurological diseases (NIND) studied as control groups. IL-15 levels were correlated with clinical parameters as duration, disability, MRI activity and clinical subtypes of the disease. RESULTS: MS patients were found to have significantly higher serum IL-15 levels compared with IND (p=0.00016) and NIND patients (p=0.00045). Elevated levels of IL-15 were also found in CSF samples from MS patients compared with patients with IND (p=0.00034) and NIND (p=0.0003). Among MS subgroups there were no statistically different IL-15 serum and CSF concentrations. No significant correlation of serum and CSF IL-15 concentrations with MRI activity, disability assessed by EDSS score and duration of the disease were also found. C/S IL-15 ratio was found lower in MS patients compared with IND (p=0.01) and not significantly different compared with NIND patients (p=0.14) suggesting that systemic activation might be the source of high CSF IL-15 levels in MS patients. CONCLUSIONS: Our findings suggest a possible role of IL-15 in the immunopathogenetic mechanisms of MS.  相似文献   

10.
Freezing of gait (FOG) is a frequent, disabling symptom of Parkinson's disease (PD). FOG usually lasts a few seconds. It refers to brief paroxysmal events during which a subject is unable to start or continue locomotion. Despite its frequency, FOG pathophysiology is unclear. Because a frontal lobe dysfunction or a disconnection between the frontal lobe and basal ganglia has been implicated in FOG, we explored frontal functions in PD patients using neuropsychological tests. Thirteen early‐stage PD patients [Hoehn & Yahr score (H&Y) ≤ 2.5] with freezing during “on ” state (FOG+), and 15 age‐, H&Y score‐, and disease‐duration‐matched PD patients without freezing (FOG?) were investigated. No patient was demented or depressed. Assessment included the Unified Parkinson's Disease Rating Scale (UPDRS), FOG questionnaire, Mini Mental State Examination (MMSE), frontal assessment battery (FAB), phonemic verbal fluency, Stroop test (parts II and III), and ten‐point clock test (TPCT). UPDRS and MMSE scores did not differ between the two groups. FAB, verbal fluency, and TPCT scores were significantly lower in FOG+ patients than in FOG? patients (FAB: P = 0.008; phonemic verbal fluency: P = 0.011; TPCT: P = 0.024). FOG correlated with lower scores at frontal tests in patients with early‐stage PD. © 2007 Movement Disorder Society  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号-23

京公网安备 11010802026262号