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

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 asse...

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Autores principales: Vesterinen, Hanna M, Currie, Gillian L, Carter, Samantha, Mee, Sarah, Watzlawick, Ralf, Egan, Kieren J, Macleod, Malcolm R, Sena, Emily S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665471/
https://www.ncbi.nlm.nih.gov/pubmed/23687965
http://dx.doi.org/10.1186/2046-4053-2-33
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author Vesterinen, Hanna M
Currie, Gillian L
Carter, Samantha
Mee, Sarah
Watzlawick, Ralf
Egan, Kieren J
Macleod, Malcolm R
Sena, Emily S
author_facet Vesterinen, Hanna M
Currie, Gillian L
Carter, Samantha
Mee, Sarah
Watzlawick, Ralf
Egan, Kieren J
Macleod, Malcolm R
Sena, Emily S
author_sort Vesterinen, Hanna M
collection PubMed
description 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.
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spelling pubmed-36654712013-05-29 Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke Vesterinen, Hanna M Currie, Gillian L Carter, Samantha Mee, Sarah Watzlawick, Ralf Egan, Kieren J Macleod, Malcolm R Sena, Emily S Syst Rev Research 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. BioMed Central 2013-05-20 /pmc/articles/PMC3665471/ /pubmed/23687965 http://dx.doi.org/10.1186/2046-4053-2-33 Text en Copyright © 2013 Vesterinen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Vesterinen, Hanna M
Currie, Gillian L
Carter, Samantha
Mee, Sarah
Watzlawick, Ralf
Egan, Kieren J
Macleod, Malcolm R
Sena, Emily S
Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title_full Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title_fullStr Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title_full_unstemmed Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title_short Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke
title_sort systematic review and stratified meta-analysis of the efficacy of rhoa and rho kinase inhibitors in animal models of ischaemic stroke
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665471/
https://www.ncbi.nlm.nih.gov/pubmed/23687965
http://dx.doi.org/10.1186/2046-4053-2-33
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