Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials

Background: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuro...

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Main Authors: Wenqiao Fu, Yin Tang, Xudong Che, Jiahe Tan, Yinrui Ma, Zhaohui He
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1009169/full
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author Wenqiao Fu
Yin Tang
Xudong Che
Jiahe Tan
Yinrui Ma
Zhaohui He
author_facet Wenqiao Fu
Yin Tang
Xudong Che
Jiahe Tan
Yinrui Ma
Zhaohui He
author_sort Wenqiao Fu
collection DOAJ
description Background: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuroprotective role in experimental animal models of stroke; however, a preclinical quantitative analysis on the ability of metformin to treat stroke is still lacking. This meta-analysis evaluates the efficacy of metformin in improving stroke prognosis in rodent models of stroke.Methods: Relevant preclinical trials were retrieved from PubMed, EMBASE, and the Web of Science. The neurological score (NS), brain water content (BWC), infarct size, rotarod test, TUNEL, neuron quantity, microglia quantity, and p-AMPK levels were compared between a control group and a metformin group using the standardized mean difference (SMD) and corresponding confidence interval (CI). Quality was assessed with SYRCLE’s risk of bias tool.Results: Fifteen articles published from 2010 to 2022 were included in the meta-analysis. The metformin group had statistically significant differences compared to the control group in the following aspects: NS (SMD −1.45; 95% CI −2.32, −0.58; p = 0.001), BWC (SMD −3.22; 95% CI −4.69, −1.76; p < 0.0001), infarct size (SMD −2.90; 95% CI −3.95, −1.85; p < 0.00001), rotarod test (SMD 2.55; 95% CI 1.87, 3.23; p < 0.00001), TUNEL (SMD -3.63; 95% CI −5.77, −1.48; p = 0.0009), neuron quantity (SMD 3.42; 95% CI 2.51, 4.34; p < 0.00001), microglia quantity (SMD −3.06; 95% CI -4.69, −1.44; p = 0.0002), and p-AMPK levels (SMD 2.92; 95% CI 2.02, 3.82; p < 0.00001). Furthermore, sensitivity analysis and stratified analysis were conducted for heterogeneous outcome indicators.Conclusion: Overall, metformin treatment improves severe outcomes triggered by stroke. Despite the limitations intrinsic to animal studies, this systematic review may provide a vital reference for future high-quality preclinical trials and clinical use.
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spelling doaj.art-3f52d9d10016425dbf86716083046e762022-12-22T03:26:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10091691009169Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trialsWenqiao Fu0Yin Tang1Xudong Che2Jiahe Tan3Yinrui Ma4Zhaohui He5Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaBackground: Stroke, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH), remains a leading cause of mortality globally. Different stroke subtypes have similar detrimental effects in multiple fields of health. Previous research has shown that metformin plays a neuroprotective role in experimental animal models of stroke; however, a preclinical quantitative analysis on the ability of metformin to treat stroke is still lacking. This meta-analysis evaluates the efficacy of metformin in improving stroke prognosis in rodent models of stroke.Methods: Relevant preclinical trials were retrieved from PubMed, EMBASE, and the Web of Science. The neurological score (NS), brain water content (BWC), infarct size, rotarod test, TUNEL, neuron quantity, microglia quantity, and p-AMPK levels were compared between a control group and a metformin group using the standardized mean difference (SMD) and corresponding confidence interval (CI). Quality was assessed with SYRCLE’s risk of bias tool.Results: Fifteen articles published from 2010 to 2022 were included in the meta-analysis. The metformin group had statistically significant differences compared to the control group in the following aspects: NS (SMD −1.45; 95% CI −2.32, −0.58; p = 0.001), BWC (SMD −3.22; 95% CI −4.69, −1.76; p < 0.0001), infarct size (SMD −2.90; 95% CI −3.95, −1.85; p < 0.00001), rotarod test (SMD 2.55; 95% CI 1.87, 3.23; p < 0.00001), TUNEL (SMD -3.63; 95% CI −5.77, −1.48; p = 0.0009), neuron quantity (SMD 3.42; 95% CI 2.51, 4.34; p < 0.00001), microglia quantity (SMD −3.06; 95% CI -4.69, −1.44; p = 0.0002), and p-AMPK levels (SMD 2.92; 95% CI 2.02, 3.82; p < 0.00001). Furthermore, sensitivity analysis and stratified analysis were conducted for heterogeneous outcome indicators.Conclusion: Overall, metformin treatment improves severe outcomes triggered by stroke. Despite the limitations intrinsic to animal studies, this systematic review may provide a vital reference for future high-quality preclinical trials and clinical use.https://www.frontiersin.org/articles/10.3389/fphar.2022.1009169/fullmetforminstrokeneuropharmacologyanimal modelsmeta-analysis
spellingShingle Wenqiao Fu
Yin Tang
Xudong Che
Jiahe Tan
Yinrui Ma
Zhaohui He
Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
Frontiers in Pharmacology
metformin
stroke
neuropharmacology
animal models
meta-analysis
title Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
title_full Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
title_fullStr Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
title_full_unstemmed Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
title_short Neuropharmacological efficacy of metformin for stroke in rodents: A meta-analysis of preclinical trials
title_sort neuropharmacological efficacy of metformin for stroke in rodents a meta analysis of preclinical trials
topic metformin
stroke
neuropharmacology
animal models
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1009169/full
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