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Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis

ABSTRACT: 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.

SUBMITTER: Tan J

PROVIDER: S-EPMC9277348 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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: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.

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Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis

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