Dataset Information

Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke.

ABSTRACT:

Background

There 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.

Methods

We 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.

Results

We 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.

Conclusions

RhoA 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.

SUBMITTER: Vesterinen HM

PROVIDER: S-EPMC3665471 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke.

Vesterinen Hanna M HM Currie Gillian L GL Carter Samantha S Mee Sarah S Watzlawick Ralf R Egan Kieren J KJ Macleod Malcolm R MR Sena Emily S ES

Systematic reviews 20130520

<h4>Background</h4>There 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.<h4>Methods</h4>We conducted a sys ...[more]

PMID: 23687965

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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.

Dataset Information

Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke.

Background

Methods

Results

Conclusions

Publications

Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke.

Similar Datasets

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