ReviewJournal of stroke2019
tPA Helpers in the Treatment of Acute Ischemic Stroke: Are They Ready for Clinical Use?
Review in Journal of stroke, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 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
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 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
- Neuroprotective Effects of Conditioned Medium of Mesenchymal Stem Cells (MSC-CM) as a Therapy for Ischemic Stroke Recovery: A Systematic Review.Neurochemical research · 2023Pooled it
- 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
- Adjuvant therapy with total salvianolic acid injection enhances the safety and efficacy of recombinant prourokinase in ischemic stroke by mitigating blood-brain barrier disruption.Journal of translational medicine · 2026Article
- Cinchonidine, a Natural Quinoline Alkaloid, Attenuates Ischemic Neurovascular Injury Through Blood-Brain Barrier Preservation.Biomedicines · 2026Article
- Multiscale photoacoustic imaging of stroke in preclinical models and future directions toward clinical translation [Invited].Biomedical optics express · 2026Review
- Adeno-associated virus-mediated inhibition of ROCK2 promotes synaptogenesis and neurogenesis in rats after ischemic stroke.Neural regeneration research · 2026Article
- Review: Systemic inflammation after stroke. Therapy and perspective.GeroScience · 2026Review
- Bridging Inflammation and Repair: The Promise of MFG-E8 in Ischemic Stroke Therapy.International journal of molecular sciences · 2025Review
- Matrix metalloproteinase‑9 in hemorrhagic transformation after acute ischemic stroke (Review).Molecular medicine reports · 2025Review
- Dehydrocostus Lactone Inhibits Microglia-Mediated Neuroinflammation by Targeting CYP2A6 to Improve Ischemic Brain Injury.CNS neuroscience & therapeutics · 2025Article
- New Wine in an Old Bottle: tPA for Ischemic Stroke Management.Translational stroke research · 2025Article
- Neutrophils: Linking Inflammation to Thrombosis and Unlocking New Treatment Horizons.International journal of molecular sciences · 2025Review
- Hospital Patient Demographics and Administration of Intravenous Thrombolysis in Acute Ischemic Stroke.JAMA network open · 2025Article
- Dual role of vascular endothelial growth factor-C in post-stroke recovery.The Journal of experimental medicine · 2025Article
- Mechanisms of QiShenYiQi in Inhibiting Blood-Brain Barrier Damage Following Stroke: A Network Pharmacology and Experimental Study.Combinatorial chemistry & high throughput screening · 2025Article
- Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.Zoological research · 2024Article
- Sanhua Tang protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and experiments.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Nicotine Treatment Ameliorates Blood-Brain Barrier Damage After Acute Ischemic Stroke by Regulating Endothelial Scaffolding Protein Pdlim5.Translational stroke research · 2024Article
- The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
5 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
1 author at 1 institution in 1 country.
Funding
Abstract
Tissue plasminogen activator (tPA) is the only therapeutic agent approved to treat patients with acute ischemic stroke. The clinical benefits of tPA manifest when the agent is administered within 4.5 hours of stroke onset. However, tPA administration, especially delayed administration, is associated with increased intracranial hemorrhage (ICH), hemorrhagic transformation (HT), and mortality. In the ischemic brain, vascular remodeling factors are upregulated and microvascular structures are destabilized. These factors disrupt the blood brain barrier (BBB). Delayed recanalization of the vessels in the presence of relatively matured infarction appears to damage the BBB, resulting in HT or ICH, also known as reperfusion injury. Moreover, tPA itself activates matrix metalloproteases, further aggravating BBB disruption. Therefore, attenuation of edema, HT, or ICH after tPA treatment is an important therapeutic strategy that may enable clinicians to extend therapeutic time and increase the probability of excellent outcomes. Recently, numerous agents with various mechanisms have been developed to interfere with various steps of ischemia/ reperfusion injuries or BBB destabilization. These agents successfully reduce infarct volume and decrease the incidence of ICH and HT after delayed tPA treatment in various animal stroke models. However, only some have entered into clinical trials; the results have been intriguing yet unsatisfactory. In this narrative review, I describe such drugs and discuss the problems and future directions. These "tPA helpers" may be clinically used in the future to increase the efficacy of tPA in patients with acute ischemic stroke.
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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.