ArticlePloS one2014
Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Cerebral Ischemia-Reperfusion Injury: Unraveling the Mitophagy-Oxidative Stress Axis for Neuroprotective Strategies.International journal of molecular sciences · 2026Review
- Edaravone: Advances on cytoprotective effects, pharmacological properties, and mechanisms of action.Pharmacological reviews · 2026Review
- A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system.Nature biomedical engineering · 2025Article
- Impaired post-stroke collateral circulation in sickle cell anemia mice.Frontiers in neurology · 2023Article
- Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia.Neurobiology of disease · 2022Article
- Monitoring the apical growth characteristics of hairy roots using non-invasive laser speckle contrast imaging.Engineering in life sciences · 2022Article
- Influence of Lower Extremity Deep Venous Thrombosis in Cerebral Infarction on Coagulation Index and Thromboelastogram and Its Risk Factors.Journal of healthcare engineering · 2022Article
- Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke.Neural regeneration research · 2021Article
- A murine photothrombotic stroke model with an increased fibrin content and improved responses to tPA-lytic treatment.Blood advances · 2020Article
- IMM-H004 Protects against Cerebral Ischemia Injury and Cardiopulmonary Complications via CKLF1 Mediated Inflammation Pathway in Adult and Aged Rats.International journal of molecular sciences · 2019Article
- Article
- Diabetic aggravation of stroke and animal models.Experimental neurology · 2017Review
- Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke.International journal of molecular sciences · 2016Review
- Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.CNS neuroscience & therapeutics · 2016Article
- Alteration of SLP2-like immunolabeling in mitochondria signifies early cellular damage in developing and adult mouse brain.The European journal of neuroscience · 2016Article
- A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia.Journal of visualized experiments : JoVE · 2015Article
- Article
- Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.Molecular and cellular biology · 2015Article
- Towards reperfusion-centric preclinical stroke research: outside the box of "reperfusion injury".Neural regeneration research · 2015Article
- Anti-tissue plasminogen activator (tPA) as an effective therapy of neonatal hypoxia-ischemia with and without inflammation.CNS neuroscience & therapeutics · 2015Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.