ReviewJournal of stroke2017
Strategies to Extend Thrombolytic Time Window for Ischemic Stroke Treatment: An Unmet Clinical Need.
Review in Journal of stroke, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review.Open veterinary journal · 2026Pooled it
- A Systematic Review and Meta-Analysis of Animal Studies Testing Intra-Arterial Chilled Infusates After Ischemic Stroke.Frontiers in neurology · 2020Pooled it
- Stem Cell-Based Therapies via Different Administration Route for Stroke: A Meta-analysis of Comparative Studies.Cell transplantationPooled it
- Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.Stroke · 2024Trial
- Trial
- Trial
- Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.Annals of neurology · 2020Trial
- Von Willebrand factor A1 blockade prevents platelet-mediated sustained occlusion for the treatment of arterial thrombosis.Communications biology · 2026Article
- Neurovascular Unit-Derived Extracellular Vesicles as Regulators of Post-Stroke Pathology and Neurorestoration.Biomolecules · 2026Review
- Amelioration of Post-Stroke Edema and Microcirculatory Dysfunction via Targeted AQP4 Inhibition While Preserving the Glymphatic System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microcirculatory failure after successful recanalization in ischemic stroke: insights into mechanisms, imaging, and therapeutic strategies.Frontiers in pharmacology · 2026Review
- DL-3-n-Butylphthalide Protects Mitochondria Against Ischemia/Hypoxia Damage via Suppressing GCN5L1-Mediated Drp1 Acetylation in Neurons and Mouse Brains.CNS neuroscience & therapeutics · 2025Article
- Brain targeted lipid nanoparticles with Hv1 inhibitors alleviate neuroinflammation post-ischemic stroke.Journal of nanobiotechnology · 2025Article
- Shengui Sansheng San alleviates the worsening of blood-brain barrier integrity resulted from delayed tPA administration through VIP/VIPR1 pathway.Chinese medicine · 2025Article
- Suppressing the Inflammatory Prostaglandin Signaling after Thrombotic Stroke Ameliorates Ischemic Brain Injury and Facilitates Poststroke Recovery.ACS pharmacology & translational science · 2024Article
- A mathematical model of plasmin-mediated fibrinolysis of single fibrin fibers.PLoS computational biology · 2024Article
- Role of transcription factors, noncoding RNAs, epitranscriptomics, and epigenetics in post-ischemic neuroinflammation.Journal of neurochemistry · 2024Review
- Protective Effect of Protocatechuic Aldehyde on Cerebral Ischemia/Reperfusion Injury in Rats through Blood-Brain Barrier Protection.Bulletin of experimental biology and medicine · 2024Article
- Differences in Acute Expression of Matrix Metalloproteinases-9, 3, and 2 Related to the Duration of Brain Ischemia and Tissue Plasminogen Activator Treatment in Experimental Stroke.International journal of molecular sciences · 2024Article
- Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment. We reviewed the pharmacological agents which reduced the risk of HT associated with delayed (beyond 4.5 hours post-stroke) tPA treatment in preclinical studies, which we classified into those that putatively preserve the blood-brain barrier (e.g., minocycline, cilostazol, fasudil, candesartan, and bryostatin) and/or enhance vascularization and protect the cerebrovasculature (e.g., coumarin derivate IMM-H004 and granulocyte colony-stimulating factor). Recently, other new therapeutic modalities (e.g., oxygen transporters) have been reported which improved delayed tPA-associated outcomes by acting through other mechanisms. While the above-mentioned interventions unequivocally reduced delayed tPA-induced HT in stroke models, the long-term efficacy of these drugs are not yet established. Further optimization is required to expedite their future clinical application. The findings from this review indicate the need to explore the most ideal adjunctive interventions that will not only reduce delayed tPA-induced HT, but also preserve neurovascular functions. While waiting for the next breakthrough drug in acute stroke treatment, it is equally important to allocate considerable effort to find approaches to address the limitations of the only FDA-approved stroke therapy.
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What OpenQuestion holds
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.