ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Granulocyte colony-stimulating factor attenuates delayed tPA-induced hemorrhagic transformation in ischemic stroke rats by enhancing angiogenesis and vasculogenesis.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.Scientific reports · 2016Pooled it
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- Review
- Mechanisms of Postischemic Stroke Angiogenesis: A Multifaceted Approach.Journal of inflammation research · 2024Review
- The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke.Neural regeneration research · 2021Article
- Colony-Stimulating Factors on Mobilizing CD34Frontiers in pharmacology · 2021Review
- Can miRNAs Be Considered as Diagnostic and Therapeutic Molecules in Ischemic Stroke Pathogenesis?-Current Status.International journal of molecular sciences · 2020Review
- Stroke gets in your eyes: stroke-induced retinal ischemia and the potential of stem cell therapy.Neural regeneration research · 2020Review
- Insights into the dual role of angiogenesis following stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- The Dynamics of Microglial Polarization Reveal the Resident Neuroinflammatory Responses After Subarachnoid Hemorrhage.Translational stroke research · 2020Article
- Article
- Dynamic Detection of Thrombolysis in Embolic Stroke Rats by Synchrotron Radiation Angiography.Translational stroke research · 2019Article
- Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation.Journal of cellular physiology · 2019Article
- Drug-like delivery methods of stem cells as biologics for stroke.Expert opinion on drug delivery · 2019Review
- tPA Helpers in the Treatment of Acute Ischemic Stroke: Are They Ready for Clinical Use?Journal of stroke · 2019Review
- Endothelial Progenitor Cells Modulate Inflammation-Associated Stroke Vasculome.Stem cell reviews and reports · 2019Article
- Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches.European journal of pharmacology · 2018Review
- Review
- Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke.International journal of molecular sciences · 2018Article
- Impact of Bone Fracture on Ischemic Stroke Recovery.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Treatment with tissue plasminogen activator (tPA) beyond the therapeutic time window (>4.5 hours post stroke) may produce hemorrhagic transformation (HT). Strategies that could extend the narrow time window of tPA will benefit a significant number of stroke patients. Male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAo) and given vehicle, tPA (10 mg/kg), or tPA and granulocyte colony-stimulating factor (G-CSF, 300 μg/kg), at 6 hours after MCAo. Twenty-four hours post treatment, G-CSF+tPA-treated stroke rats displayed 25% improvement in neurological functions and 38.9% reduction of hemorrhage, with Western blots showing 1.9- and 1.2-fold increments in Ang-2 expression in the ischemic cortex and striatum, respectively, and 3-fold increase in phosphorylated endothelial nitric oxide synthase expression in the ipsilateral cortex relative to tPA-treated rats. Immunohistochemistry also showed 2- and 2.8-fold increase in von-Willebrand expression, 3.2- and 2.2-fold increased CD34+ expression, and 4- and 13-fold upregulation of VEGFR-2 expression in the ischemic cortex and striatum, respectively, in G-CSF+tPA-treated stroke rats relative to tPA-treated subjects. Altogether, these findings indicate that G-CSF attenuated delayed tPA-induced HT likely via the enhancement of angiogenesis and vasculogenesis. The use of G-CSF to protect the vasculature may improve the clinical outcome of tPA even outside the currently indicated therapeutic window for ischemic stroke.
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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.