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Neural Regeneration Research Jul 2024Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may...
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
PubMed: 38051903
DOI: 10.4103/1673-5374.387976 -
Neuroscience and Biobehavioral Reviews Sep 2022Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine... (Meta-Analysis)
Meta-Analysis Review
Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine oxidase B (MAOB), which causes oxidative stress and destroys dopaminergic (DA) neurons in substantia nigra pars compacta (SNc) and is widely used to create animal models of PD. However, to-date, a comprehensive analysis of the MPTP effects on various aspects of PD does not exist. Here, we provide a systematic review and meta-analysis on the MPTP effects on memory and motor functions by analyzing 51 studies on more than one thousand animals mainly including rats and mice. The results showed that in addition to motor functions such as coordination, balance and locomotor activity, MPTP significantly affects various mnemonic processes including spatial memory, working memory, recognition memory, and associative memory compared with the control group with some differences between systemic and intra-nigral injections on spatial memory, familiar object recognition, and anxiety-like behaviors. Nevertheless, our analysis failed to find systematic relationship between MPTP injection protocol parameters reported and the extent of the induced PD symptoms that can be a cause of concern for replicability of MPTP studies.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Cognition; Disease Models, Animal; Mice; Parkinson Disease; Pyrrolidines; Rats; Rodentia
PubMed: 35872230
DOI: 10.1016/j.neubiorev.2022.104792 -
Neurophysiologie Clinique = Clinical... Apr 2019Parkinson's disease (PD) is known to have a long prodromal stage due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta over the course of...
Parkinson's disease (PD) is known to have a long prodromal stage due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta over the course of many years without clinical manifestations of PD. When the diagnosis is made, the neuropathological process is already well entrenched. Consequently, identifying individuals during this prodromal period could be very helpful for future trials of neuroprotective or disease-modifying therapies, which might slow or prevent the degeneration of dopaminergic neurons. Thus, efforts are needed to determine appropriate early markers of PD. Gait and balance disorders are frequent during the early stages of PD. This systematic review aims to determine if gait and balance disorders occur before the diagnosis of PD and if so, whether they could be used as markers of preclinical PD. Findings reveal that, at the presymptomatic stage of PD, impaired basal ganglia function leads to disorders in gait and balance. Both clinical and instrumental assessments allow early detection of these disorders, particularly when performed under challenging conditions (e.g. dual-task). Among all studied parameters, temporal gait variability and arm kinematics appear to be promising markers of preclinical PD.
Topics: Biomarkers; Early Diagnosis; Gait Disorders, Neurologic; Humans; Locomotion; Parkinson Disease; Postural Balance
PubMed: 30686671
DOI: 10.1016/j.neucli.2019.01.001 -
Journal of Neurology Dec 2021To evaluate the diagnostic performance of iron-sensitive sequences targeting the substantia nigra for distinguishing patients with Parkinson's disease from control... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the diagnostic performance of iron-sensitive sequences targeting the substantia nigra for distinguishing patients with Parkinson's disease from control participants and to identify factors causing heterogeneity.
METHODS
A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before March 6, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Subgroup and meta-regression analyses were also performed to determine factors influencing heterogeneity affecting the diagnostic performance among the clinical, MRI, and analytic characteristics.
RESULTS
A total of 22 articles including 1126 patients with Parkinson's disease and 933 control participants were enrolled in this systematic review and meta-analysis. Of those, 12 studies used objective analyses of quantitative susceptibility measurements, and 10 visually assessed the nigrosome-1 in subjective analyses. Iron-sensitive nigral magnetic resonance imaging showed a pooled sensitivity of 92% (95% confidence interval 88-95%) and a pooled specificity of 90% (95% confidence interval 81-95%). According to subgroup and meta-regression analyses, a longer mean disease duration in patients with Parkinson's disease (≥ 5 years), subjective analysis, a smaller size of pixel (< 0.6 mm), a larger flip angle (> 15°), a smaller slice thickness (≤ 1 mm), and specific targeting of the substantia nigra pars compacta improved the diagnostic performance.
CONCLUSION
Iron-sensitive nigral magnetic resonance imaging had a favorable diagnostic performance in discriminating patients with Parkinson's disease from control participants. Subjective analytic methods remain superior to objective approaches. Further improvements of the spatial resolution and contrast-to-noise ratio to specifically target the nigrosome-1 with objective analytic methods will be needed.
Topics: Humans; Iron; Magnetic Resonance Imaging; Parkinson Disease; Sensitivity and Specificity; Substantia Nigra
PubMed: 33914142
DOI: 10.1007/s00415-021-10582-x -
International Journal of Molecular... Sep 2022Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies... (Review)
Review
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
Topics: Biomarkers; Dopamine; Dopaminergic Neurons; Extracellular Vesicles; Humans; MicroRNAs; Parkinson Disease; Proteomics; RNA, Long Noncoding; alpha-Synuclein
PubMed: 36232833
DOI: 10.3390/ijms231911508 -
Cureus Sep 2021Parkinson's disease (PD), a neurodegenerative disorder, is caused due to the loss of dopaminergic neurons in substantia nigra pars compacta, and it mainly affects the... (Review)
Review
Parkinson's disease (PD), a neurodegenerative disorder, is caused due to the loss of dopaminergic neurons in substantia nigra pars compacta, and it mainly affects the motor function of the diseased individual. The most effective treatment for PD to date is levodopa, the precursor molecule for dopamine which ultimately helps overcome the loss of dopamine in the brain. However, long-term levodopa therapy significantly impairs patients' quality of life by causing various disabling motor and non-motor complications. We conducted this study intending to review the available literature that has compared the efficacy and safety of continuous subcutaneous apomorphine infusion (CSAI) with other available treatment options like deep brain stimulation, intestinal levodopa gel, and oral dopaminergic agents. We searched PubMed, Embase, and Scopus databases using the appropriate search strategy. The studies which compared the safety and efficacy of continuous subcutaneous apomorphine infusion to other available treatment options in advanced Parkinson's disease were included in our study. The bias assessment of the studies was done using Cochrane Risk of Bias 2.0 tool for randomized controlled trials, Risk of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool for non-randomized interventional studies, and Joanna Briggs Institute Critical Appraisal tools (JBI) for cohort studies. We included eight articles in our systematic review including a randomized controlled trial. None of the included studies had a high risk of bias. We found that in patients with advanced Parkinson's, CSAI demonstrated definite improvement in off-time duration. CSAI has also been shown to improve various non-motor functions, including neuropsychiatric problems in these patients. CSAI has demonstrated safety and efficacy in patients with advanced Parkinson's disease. However, the decision-making is multifactorial. Hence, further studies are required that directly compare the available treatment options with one another and study their overall effects on patients' quality of life.
PubMed: 34660137
DOI: 10.7759/cureus.17949 -
Medicine Nov 2017Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative stress is proposed to play a critical role in the pathogenesis of PD. Uric acid (UA), as an important physiological antioxidant, is identified a molecular predictor associated with a decreased risk and a slower disease progression for PD and potential neuroprotectant of PD by increasing epidemiological and clinical evidences. Within this review, we will present a comprehensive overview of the data linking UA to PD in recent years.
METHODS
We searched PubMed, EMBASE, Web of Science databases for relevant studies. Any observational or experimental studies that evaluated UA and PD were our goal of searching the electric databases.
RESULTS
Twelve studies that evaluated UA and PD were identified in this review. We reviewed the roles of UA in the pathogenesis of PD, the association of UA with morbidity, severity/progression, nonmotor symptoms, motor complications of PD, with an attempt to provide new ideas for diagnosis and treatment in PD.
CONCLUSION
Our findings supported that lots of clinical and epidemiological data observed lower UA levels in PD patients. Manipulation of UA or its precursors' concentration could be effective to treat or prevent PD. However, it is still suspectable that higher UA levels are better enough to PD patients. Furthermore, for the complex nature of PD and its heterogeneous genetic and environmental influences, it is inadequate for just manipulating UA in treating the disease.
Topics: Humans; Age Factors; Biomarkers; Disease Progression; Hyperuricemia; Movement Disorders; Oxidative Stress; Parkinson Disease; Severity of Illness Index; Sex Factors; Uric Acid
PubMed: 29137045
DOI: 10.1097/MD.0000000000008502 -
Neurological Sciences : Official... Dec 2019The main purpose of this study was to systematically evaluate the accuracy of neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in Parkinson's disease (PD)... (Meta-Analysis)
Meta-Analysis
The main purpose of this study was to systematically evaluate the accuracy of neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in Parkinson's disease (PD) diagnosis using a meta-analysis method. In PubMed, Web of Science, Embase, and Google Scholar, the literatures were searched for the diagnostic value of neuromelanin-sensitive magnetic resonance imaging in PD. The literatures were screened in the light of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data analysis was processed by Stata 12.0 software to obtain meta-analysis, heterogeneity analysis, and publication bias. Meta-analysis results showed by using NM-MRI observed substantia nigra pars compacta (SNpc) on PD, the pooled diagnostic sensitivity and specificity were 0.82 (95% CI, 0.74-0.87) and 0.82 (95% CI, 0.73-0.89), respectively. And the pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 4.58 (95% CI, 3.08-6.82) and 0.22 (95% CI, 0.16-0.31), respectively. Moreover, subgroup analysis according to the measurement criteria of SNpc showed the SNpc volume should be used as good a marker for diagnosing PD. Finally, Fagan test demonstrated that when PLR was equal to 5, the posterior probability is significantly enhanced to 53%, compared with prior probability (20%). As for NLR (0.22), the prior probability is 20%, while the posterior probability remarkably dropped to 5%. In conclusion, SNpc signal detected by NM-MRI exhibited high sensitivity and specificity for diagnosis of PD, which was a high-performance imaging diagnostic method for PD. We recommend NM-MRI imaging technology to be widely used in Parkinson's diagnosis.
Topics: Humans; Magnetic Resonance Imaging; Melanins; Neuroimaging; Parkinson Disease; Substantia Nigra
PubMed: 31392640
DOI: 10.1007/s10072-019-04014-y -
NeuroImage. Clinical 2013There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials....
There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results. To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes. We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10(- 3) mm(2)/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I(2) = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I(2) = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = - 0.5, p = 0.22, I(2) = 28%). The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson's disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker.
PubMed: 24273730
DOI: 10.1016/j.nicl.2013.10.006 -
Frontiers in Aging Neuroscience 2020Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models...
Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models of Parkinson's disease (PD). However, their pooled effects for dopaminergic neuron have yet to be described. To review the neuroprotective effect of naïve BMSCs in rodent models of PD. The PubMed, EMBASE, and Web of Science databases were searched up to September 30, 2020. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified BMSCs; (3) comparison: not specified; (4) primary outcome: tyrosine hydroxylase level in the substantia nigra pars compacta and rotational behavior; secondary outcome: rotarod test, and limb function; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis. Twenty-seven animal studies were included. The median quality score was 4.7 (interquartile range, 2-8). Overall standardized mean difference between animals treated with naïve BMSCs and controls was 2.79 (95% confidence interval: 1.70, 3.87; < 0.001) for densitometry of tyrosine hydroxylase-positive staining; -1.54 (95% confidence interval: -2.11, -0.98; < 0.001) for rotational behavior. Significant heterogeneity among studies was observed. Results of this meta-analysis suggest that naïve BMSCs therapy increased dopaminergic neurons and ameliorated behavioral deficits in rodent models of PD.
PubMed: 33362527
DOI: 10.3389/fnagi.2020.539933