ArticleNature medicine2008
Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers, 1 of them a synthesis that pooled it.
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Who cites it
251 citing papers in PubMed, 1 synthesis or guideline pooled it, 468 citations in OpenAlex.
- Efficacy and safety of imatinib in patients with COVID-19: a systematic review and meta-analysis.Wiener klinische Wochenschrift · 2025Pooled it
- Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial.BMC medicine · 2024Trial
- Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis.Journal of internal medicine · 2017Trial
- Article
- The dilemma of thromboprophylaxis in stroke patients.Clinical medicine (London, England) · 2026Review
- An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.Investigative ophthalmology & visual science · 2026Article
- Cocaine Use Disorder: Neuropathology and Exploratory Treatments.Molecular neurobiology · 2026Review
- Fibrinolysis-unrelated functions of the plasminogen/plasmin system: A gateway to successful parasitism?Current research in parasitology & vector-borne diseases · 2026Review
- Platelet-membrane-coated nanoparticles enable safe and targeted thrombolysis with preserved neurovascular integrity.Frontiers in pharmacology · 2026Article
- Ultrafine Molybdenum Wire Braided Neurointerventional Implants: Bridging Biodegradability and Neurovascular Safety for Stroke Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- Tissue Plasminogen Activator as an Approved Strategy for Ischemic Stroke: A Review of tPA's Structure, Mechanism of Action and the Novel Targeting Methods.Journal of molecular neuroscience : MN · 2025Review
- Article
- Matrix metalloproteinase‑9 in hemorrhagic transformation after acute ischemic stroke (Review).Molecular medicine reports · 2025Review
- Micrometer-scale tPA beads amplify plasmin generation for enhanced thrombolytic therapy.Bioengineering & translational medicine · 2025Article
- PA System in the Pathogenesis of Ischemic Stroke.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Imatinib on target in stroke recovery.The Journal of clinical investigation · 2025Article
- The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.Journal of neuroinflammation · 2025Article
- MgSOTheranostics · 2025Article
- Thrombolysis exacerbates cerebrovascular injury after ischemic stroke via a VEGF-B dependent effect on adipose lipolysis.bioRxiv : the preprint server for biology · 2024Article
191 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is markedly limited owing to concerns about hemorrhagic complications and the requirement that tPA be administered within 3 h of symptoms. Here we report that tPA activation of latent platelet-derived growth factor-CC (PDGF-CC) may explain these limitations. Intraventricular injection of tPA or active PDGF-CC, in the absence of ischemia, leads to significant increases in cerebrovascular permeability. In contrast, co-injection of neutralizing antibodies to PDGF-CC with tPA blocks this increased permeability, indicating that PDGF-CC is a downstream substrate of tPA within the neurovascular unit. These effects are mediated through activation of PDGF-alpha receptors (PDGFR-alpha) on perivascular astrocytes, and treatment of mice with the PDGFR-alpha antagonist imatinib after ischemic stroke reduces both cerebrovascular permeability and hemorrhagic complications associated with late administration of thrombolytic tPA. These data demonstrate that PDGF signaling regulates blood-brain barrier permeability and suggest potential new strategies for stroke treatment.
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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.