Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis.
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ABSTRACT:
SUBMITTER: Cui HJ
PROVIDER: S-EPMC4441464 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC7880339 | biostudies-literature
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.
| S-EPMC8446273 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX) therapy appears to be effective for ICH. The aim of this study was to perform a systematic review of DFX therapy for ICH patients and evaluate the efficacy and safety of DFX therapy for ICH patients. We searched Medline, Embase, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, all Chinese databases and the reference lists of all included studies and review articles. We then performed a systematic review of studies involving the administration of DFX following ICH. Only two studies were included, a prospective, randomized clinical trial and a prospective,observational cohort study with concurrent groups. Qualitative analysis of each study revealed one randomized controlled trial of moderate quality with a moderate risk of bias and one observational cohort study of moderate quality with a moderate risk of bias. DFX may be an effective treatment for edema in patients with ICH. However, due to the small number of trials and small sample sizes of these trials, insufficient evidence exists to determine the effect of DFX on neurologic outcomes after ICH and the safety of this intervention. Further investigation is required before DFX can become a routine treatment for ICH.
| S-EPMC5863956 | biostudies-literature
Project description:Background: Subarachnoid hemorrhage (SAH) is a serious neurosurgical emergency with extremely high morbidity and mortality rates. Resveratrol (RES), a natural polyphenolic phytoalexin, is broadly presented in a wide variety of plants. Previous research had reasonably revealed its neuroprotective effects on experimental SAH animal models to some extent. But the results were more controversial. Therefore, we conducted a meta-analysis to evaluate the evidence on the effectiveness of RES in improving outcomes in SAH animal models. Methods: A systematic literature review was conducted in PubMed, EMBASE, and Web of Science databases to incorporate experimental control studies on the efficacy of RES on SAH models into our research. The standardized mean difference (SMD) was used to compare the brain water content (BWC) and neurological score (NS) between the treatment and control groups. Results: Overall, 16 articles published from 2014 to 2022 met the inclusion criteria. The meta-analysis of BWC showed a significant difference in favor of RES treatment (SMD: -1.026; 95% CI: -1.380, -0.672; p = 0.000) with significant heterogeneity (Q = 84.97; I2 = 60.0%; p = 0.000). Further stratified analysis was performed for methodological differences, especially dosage, time of treatments, and time-point of outcome assessment. The meta-analysis of NS showed a significant difference in favor of RES treatment (SMD: 1.342; 95% CI: 1.089, 1.595; p = 0.000) with low heterogeneity (Q = 25.58; I2 = 17.9%; p = 0.223). Conclusion: Generally, RES treatment showed an improvement in both pathological and behavioral outcomes in SAH animal models. The results of this study may provide a reference for preclinical and clinical studies in the future to some extent, with great significance for human health.
| S-EPMC9277348 | biostudies-literature
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.
| S-EPMC6247734 | biostudies-literature
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.
| S-EPMC9446670 | biostudies-literature
Project description:Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals.
| S-EPMC5046161 | biostudies-literature
Project description:BackgroundThere is currently only one clinically approved drug, tissue plasminogen activator (tPA), for the treatment of acute ischaemic stroke. The RhoA pathway, including RhoA and its downstream effector Rho kinase (ROCK), has been identified as a possible therapeutic target. Our aim was to assess the impact of study design characteristics and study quality on reported measures of efficacy and to assess for the presence and impact of publication bias.MethodsWe conducted a systematic review and meta-analysis on publications describing the efficacy of RhoA and ROCK inhibitors in animal models of focal cerebral ischaemia where outcome was assessed as a change in lesion size or neurobehavioural score, or both.ResultsWe identified 25 published papers which met our inclusion criteria. RhoA and ROCK inhibitors reduced lesion size by 37.3% in models of focal cerebral ischaemia (95% CI, 28.6% to 46.0%, 41 comparisons), and reduced neurobehavioural data by 40.5% (33.4% to 47.7%, 30 comparisons). Overall study quality was low (median=4, interquartile range 3-5) and measures to reduce bias were seldom reported. Publication bias was prevalent and associated with a substantial overstatement of efficacy for lesion size.ConclusionsRhoA and ROCK inhibitors appear to be effective in animal models of stroke. However the low quality score, publication bias and limited number of studies are areas which need attention prior to conducting clinical trials.
| S-EPMC3665471 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD?=?0.59, 95% CI?=?0.51-0.68, P?<?0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD?=?-0.03, 95% CI?=?-0.13-0.06, P?>?0.05); further subgroup analysis of ethnicity (Asians: SMD?=?0.57, 95% CI?=?0.48-0.66, P?<?0.001; Caucasians: SMD?=?0.77, 95% CI?=?0.51-1.02, P?<?0.001) and sample size (small samples: SMD?=?0.55, 95% CI?=?0.30-0.80, P?<?0.001; large samples size: SMD?=?0.60, 95% CI?=?0.51-0.69, P?<?0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.
| S-EPMC5803270 | biostudies-other
Project description:BACKGROUND:Breast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer. METHODS:We searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias. RESULTS:We included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%). Median survival was prolonged by a factor of 1.45 (1.30-1.62). Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias. CONCLUSION:We have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.
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