The Protective Role of Immunomodulators on Tissue-Type Plasminogen Activator-Induced Hemorrhagic Transformation in Experimental Stroke: A Systematic Review and Meta-Analysis

Background: Recanalization with tissue plasminogen activator (tPA) is the only approved agent available for acute ischemic stroke. But delayed treatment of tPA may lead to lethal intracerebral hemorrhagic transformation (HT). Numerous studies have reported that immunomodulators have good efficacy on tPA-induced HT in ischemic stroke models. The benefits of immunomodulators on tPA-associated HT are not clearly defined. Here, we sought to conduct a systematic review and meta-analysis of preclinical studies to further evaluate the efficacy of immunomodulators.Methods: The PubMed, Web of Science, and Scopus electronic databases were searched for studies. Studies that reported the efficacy of immunomodulators on tPA-induced HT in animal models of stroke were included. Animals were divided into two groups: immunomodulators plus tPA (intervention group) or tPA alone (control group). The primary outcome was intracerebral hemorrhage, and the secondary outcomes included infarct volume and neurobehavioral score. Study quality was assessed by the checklist of CAMARADES. We used standardized mean difference (SMD) to assess the impact of interventions. Regression analysis and subgroup analysis were performed to identify potential sources of heterogeneity and evaluate the impact of the study characteristics. The evidence of publication bias was evaluated using trim and fill method and Egger’s test.Results: We identified 22 studies that met our inclusion criteria involving 516 animals and 42 different comparisons. The median quality checklist score was seven of a possible 10 (interquartile range, 6–8). Immunomodulators improved cerebral hemorrhage (1.31 SMD, 1.09–1.52); infarct volume (1.35 SMD, 0.95–1.76), and neurobehavioral outcome (0.9 SMD, 0.67–1.13) in experimental stroke. Regression analysis and subgroup analysis indicated that control of temperature and time of assessment were important factors that influencing the efficacy of immunomodulators.Conclusion: Our findings suggested that immunomodulators had a favorable effect on tPA-associated intracerebral hemorrhage, cerebral infarction, and neurobehavioral impairments in animal models of ischemic stroke.

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The impact of cerebral microbleeds on intracerebral hemorrhage and poor functional outcome of acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis

Journal of Neurology ◽

10.1007/s00415-016-8339-1 ◽

2016 ◽

Vol 264 (7) ◽

pp. 1309-1319 ◽

Cited By ~ 9

Author(s):

Shuang Wang ◽

Yan Lv ◽

Xin Zheng ◽

Jing Qiu ◽

Hui-Sheng Chen

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Meta Analysis ◽

Intravenous Thrombolysis ◽

Stroke Patients ◽

Poor Functional Outcome ◽

The Impact

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A Systematic Review and Meta-Analysis of Erythropoietin in Experimental Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2009.267 ◽

2009 ◽

Vol 30 (5) ◽

pp. 961-968 ◽

Cited By ~ 63

Author(s):

Mikael Jerndal ◽

Kalle Forsberg ◽

Emily S Sena ◽

Malcolm R Macleod ◽

Victoria E O'Collins ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Infarct Size ◽

Potential Benefit ◽

Focal Cerebral Ischemia ◽

Meta Analysis ◽

Experimental Stroke ◽

Inclusion Criteria ◽

The Impact ◽

Neurobehavioral Outcome

Erythropoietin (EPO) has shown promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also to promote regeneration after stroke. Here, we report a systematic review and meta-analysis of the efficacy of EPO in animal models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral outcome. Nineteen studies involving 346 animals for infarct size and 425 animals for neurobehavioral outcome met our inclusion criteria. Erythropoietin improved infarct size by 30.0% (95% CI: 21.3 to 38.8) and neurobehavioral outcome by 39.8% (33.7 to 45.9). Studies that randomized to treatment group or that blinded assessment of outcome showed lower efficacy. Erythropoietin was tested in animals with hypertension in no studies reporting infarct size and in 7.5% of the animals reporting neurobehavioral outcome. These findings show efficacy for EPO in experimental stroke, but when the impact of common sources of bias are considered, this efficacy falls, suggesting we may be overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works best would be beneficial.

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SERUM GLIAL FIBRILLARY ACIDIC PROTEIN IN THE DIFFERENTIAL DIAGNOSIS OF INTRACEREBRAL HEMORRHAGE AND ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW AND DIAGNOSTIC TEST ACCURACY META-ANALYSIS

10.26226/morressier.58e389add462b802923855f8 ◽

2017 ◽

Author(s):

Aristeidis Katsanos

Keyword(s):

Systematic Review ◽

Differential Diagnosis ◽

Ischemic Stroke ◽

Glial Fibrillary Acidic Protein ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Diagnostic Test ◽

Meta Analysis ◽

Diagnostic Test Accuracy ◽

Test Accuracy

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Efficacy of Deferoxamine in Animal Models of Intracerebral Hemorrhage: A Systematic Review and Stratified Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0127256 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0127256 ◽

Cited By ~ 24

Author(s):

Han-Jin Cui ◽

Hao-yu He ◽

A-Li Yang ◽

Hua-Jun Zhou ◽

Cong Wang ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Intracerebral Hemorrhage ◽

Meta Analysis

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EXPRESS: Impact of renal impairment on short-term outcomes following endovascular thrombectomy for acute ischemic stroke: A systematic review and meta-analysis

International Journal of Stroke ◽

10.1177/17474930211047337 ◽

2021 ◽

pp. 174749302110473

Author(s):

Jin Pyeong Jeon ◽

Chih-Hao Chen ◽

Fon-Yih Tsuang ◽

Jianming Liu ◽

Michael D Hill ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Renal Impairment ◽

Acute Ischemic Stroke ◽

Meta Analysis ◽

Functional Independence ◽

Continuous Variable ◽

Endovascular Thrombectomy ◽

Symptomatic Intracerebral Hemorrhage ◽

The Impact

Background. The impact of renal impairment (RI) on the outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims. We registered a protocol on September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. RI was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at 3 months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage (sICH). Summary of review. Eleven studies involving 3453 patients were included. For the unadjusted outcomes, RI was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39â0.62) and higher mortality (OR, 2.55; 95% CI, 2.03â3.21). RI was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63â1.00) and sICH (OR, 1.41; 95% CI, 0.95â2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45â0.77), mortality (OR, 2.23, 95% CI, 1.45â3.43), and sICH (OR, 1.34; 95% CI, 0.85â2.10). Conclusions. We presented the first systematic review to demonstrate that RI is associated with fewer functional independence and higher mortality. Future EVT studies should publish complete renal eGFR data to facilitate prognostic studies and permit eGFR to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309

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Abstract 1944: Atorvastatin Reduces Intracerebral Hemorrhage after Experimental Stroke

Circulation ◽

10.1161/circ.116.suppl_16.ii_418-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Hazem F Elewa ◽

Anna Kozak ◽

David Rychly ◽

Adviye Ergul ◽

Reginald Frye ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Methyl Cellulose ◽

The United States ◽

Experimental Stroke ◽

High Risk Population ◽

Protective Agent ◽

Oral Gavage

Ischemic stroke is a leading cause of death and disability in the United States and diabetes mellitus is the fastest growing risk factor for stroke. In addition, hyperglycemia, which is usually associated with diabetes, tends to worsen ischemia/reperfusion injury and to induce more oxidative stress damage. Preliminary data from our laboratory showed that diabetic animals (Goto-Kakizaki rats (GKs) are more susceptible to vascular damage leading to intracerebral hemorrhage. Many studies have indicated that statins possess neuroprotective properties even when administered after the onset of ischemia. However, the acute vascular effects of statins after ischemic stroke have not been studied to date. Objective: to evaluate the efficacy and magnitude of vascular protection of acute statin therapy in both GKs and their normoglycemic controls after experimental ischemic stroke. Methods: Male Wistar (W) and GK rats (270–305 g) underwent 3 hours of middle cerebral artery occlusion (MCAO) followed by reperfusion for 21 hours. Animals were randomized to receive either atorvastatin (15mg/Kg) or methyl cellulose (0.5%), administered by oral gavage, the first dose 5 minutes after reperfusion and the second dose after 12 hours. Brain tissue was analyzed for infarct volume and hemoglobin content. In another set of Wistar rats (n=3), atorvastatin (15mg/Kg) was administered by oral gavage to compare its pharmacokinetic profile with that of humans Results: Atorvastatin-treated groups had significantly lower hemoglobin (p=0.0156) and infarct volume (p=0.0132) compared to their controls. Atorvastatin peak concentration (27–77 ng/ml) in rats’ plasma was found to be similar to that seen after 80mg/day of atorvastatin in humans. Conclusion: Atorvastatin can be a novel vascular protective agent after acute ischemic stroke especially in a high risk population like diabetics. The mechanisms through which these effects are mediated are currently being investigated.

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