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Efficacy of melatonin in animal models of intracerebral hemorrhage: a systematic review and meta-analysis.

ABSTRACT: Melatonin is a potent antioxidant and anti-inflammatory agent that is showing promising results in acute brain injury. The aim of this study was to systematically evaluate the pre-clinical evidence on the effectiveness of melatonin in improving outcome after intracerebral hemorrhage (ICH). We searched mainstream databases from the inception to the end of June 2020. Outcomes were measured by neurobehavioral scores or brain water content. Meta-analyses were performed with Stata 12.0 and Review Manager 5.3. Finally, 8 articles published from 2008 to 2019 met the inclusion criteria. Meta-analysis of pre-clinical data revealed an overall positive effect on neurobehavioral outcome with a standardized mean difference (SMD) of -0.81 (95% CI: -1.47, -0.15; p = 0.016) with significant heterogeneity (Q = 41.49, I² = 68.7%; p = 0.000). Further subgroup analysis were performed from methodological differences, especially dose and timing of treatments. Furthermore, melatonin reduced cerebral edema by an SMD of -0.78 (95% CI: -1.23, -0.34; p = 0.001) with low heterogeneity. In conclusion, melatonin treatment significantly improves both behavioral and pathological outcomes in animal models of ICH. In addition, the results should be interpreted in light of the limitations in experimental design and methodological quality of the studies included in the meta-analysis.

SUBMITTER: Zeng L

PROVIDER: S-EPMC7880339 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Efficacy of melatonin in animal models of intracerebral hemorrhage: a systematic review and meta-analysis.

Zeng Liuwang L Zhu Yuwei Y Hu Xiangyu X Qin Haiyun H Tang Jiayu J Hu Zhiping Z Chen Chunli C

Aging 20210127 2

Melatonin is a potent antioxidant and anti-inflammatory agent that is showing promising results in acute brain injury. The aim of this study was to systematically evaluate the pre-clinical evidence on the effectiveness of melatonin in improving outcome after intracerebral hemorrhage (ICH). We searched mainstream databases from the inception to the end of June 2020. Outcomes were measured by neurobehavioral scores or brain water content. Meta-analyses were performed with Stata 12.0 and Review Man ...[more]

PMID: 33503014

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Project description:Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH. Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD). Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models. Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.

Project description:BackgroundPrognostic tools for intracerebral hemorrhage (ICH) patients are potentially useful for ascertaining prognosis and recommended in guidelines to facilitate streamline assessment and communication between providers. In this systematic review with meta-analysis we identified and characterized all existing prognostic tools for this population, performed a methodological evaluation of the conducting and reporting of such studies and compared different methods of prognostic tool derivation in terms of discrimination for mortality and functional outcome prediction.MethodsPubMed, ISI, Scopus and CENTRAL were searched up to 15th September 2016, with additional studies identified using reference check. Two reviewers independently extracted data regarding the population studied, process of tool derivation, included predictors and discrimination (c statistic) using a predesignated spreadsheet based in the CHARMS checklist. Disagreements were solved by consensus. C statistics were pooled using robust variance estimation and meta-regression was applied for group comparisons using random effect models.ResultsFifty nine studies were retrieved, including 48,133 patients and reporting on the derivation of 72 prognostic tools. Data on discrimination (c statistic) was available for 53 tools, 38 focusing on mortality and 15 focusing on functional outcome. Discrimination was high for both outcomes, with a pooled c statistic of 0.88 for mortality and 0.87 for functional outcome. Forty three tools were regression based and nine tools were derived using machine learning algorithms, with no differences found between the two methods in terms of discrimination (p = 0.490). Several methodological issues however were identified, relating to handling of missing data, low number of events per variable, insufficient length of follow-up, absence of blinding, infrequent use of internal validation, and underreporting of important model performance measures.ConclusionsPrognostic tools for ICH discriminated well for mortality and functional outcome in derivation studies but methodological issues require confirmation of these findings in validation studies. Logistic regression based risk scores are particularly promising given their good performance and ease of application.

Project description:BackgroundMultiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies.MethodsA literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models.ResultsThe median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was - 2.27 for mNSS, - 2.14 for rotarod test, - 2.06 for MLPT, - 1.33 for cylinder test, - 1.95 for corner turn test, - 1.42 for tissue loss, and - 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = - 2.57) compared with low-quality comparisons (SMD = - 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = - 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = - 1.84) compared with the collagenase-induced ICH model (SMD = - 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss.ConclusionsOur results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.

Project description:BackgroundAnimal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types.MethodsWe searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies.ResultsWe included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43).ConclusionThis systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages).Systematic review registrationPROSPERO-ID CRD42022308833.

Dataset Information

Efficacy of melatonin in animal models of intracerebral hemorrhage: a systematic review and meta-analysis.

Publications

Efficacy of melatonin in animal models of intracerebral hemorrhage: a systematic review and meta-analysis.

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