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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 -
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 -
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 -
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 -
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 -
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 -
Parkinsonism & Related Disorders Sep 2020There is currently no definitive diagnostic test for Parkinson's disease (PD) and the current diagnostic procedure primarily relies on clinical manifestations. A... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There is currently no definitive diagnostic test for Parkinson's disease (PD) and the current diagnostic procedure primarily relies on clinical manifestations. A hypointense appearance of nigrosome-1 (or absence of the "swallow tail" sign) on magnetic resonance imaging (MRI) has been proposed as a biomarker for PD. This meta-analysis examined the diagnostic accuracy of the appearance of nigrosome-1 on Magnetic Resonance Imaging (MRI) in differentiating idiopathic PD patients from healthy adults.
METHODS
Databases (MEDLINE, Embase, Scopus) were searched from 2012 (first publication of nigrosome-1 MRI scans) up until September 2019. Two researchers independently screened all titles and abstracts to identify studies that met the inclusion criteria and extracted relevant articles in a uniform manner. Two authors independently extracted data and assessed the risk of bias using a customized QUADAS-2 tool. Pooled sensitivity and specificity were calculated using a hierarchical summary receiver operating characteristic approach, as were positive and negative likelihood ratios.
RESULTS
Nineteen studies containing a total of 1508 participants (903 idiopathic PD patients and 605 healthy controls) were included. The overall sensitivity and specificity were 0.94 (95%CI, 0.93-0.96) and 0.90 (95%CI, 0.88-0.92), respectively. The likelihood ratios for positive and negative test results were 9.72 (95%CI, 5.58-16.04) and 0.08 (95%CI, 0.05-0.12). The pooled area under the receiver operating characteristics curve (AUC) in the diagnosis of idiopathic PD was 0.98.
CONCLUSIONS
Visual assessment of the nigrosome-1 appearance, at 3 or 7T, yields excellent diagnostic accuracy for differentiating idiopathic PD from healthy adults.
Topics: Humans; Magnetic Resonance Imaging; Parkinson Disease; Pars Compacta
PubMed: 32668370
DOI: 10.1016/j.parkreldis.2020.07.002 -
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