ArticleMolecular neurobiology2016
GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 86 citations in OpenAlex.
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- Neuroprotective effect of 3',4'-dihydroxyflavonol on blood-brain barrier ıntegrity and matrix remodeling in rats with transient bilateral carotid occlusion-ınduced ıschemia-reperfusion.Journal of bioenergetics and biomembranes · 2026Article
- ARPC1B Promotes Clear Cell Renal Cell Carcinoma Progression via the Wnt/β-Catenin Signaling Pathway.Oncology research · 2025Article
- Positive Effects of Argon Inhalation After Traumatic Brain Injury in Rats.International journal of molecular sciences · 2024Article
- Non-coding RNAs and angiogenesis in cardiovascular diseases: a comprehensive review.Molecular and cellular biochemistry · 2024Review
- Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review.International journal of medical sciences · 2024Review
- Tau and GSK-3β are Critical Contributors to α-Synuclein-Mediated Post-Stroke Brain Damage.Neuromolecular medicine · 2023Article
- A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine.Frontiers in neuroscience · 2023Review
- Bioinformatic identification of hub genesFrontiers in neuroscience · 2023Article
- A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.Heliyon · 2023Article
- GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA After Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway.Molecular neurobiology · 2022Article
- In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy.Molecules (Basel, Switzerland) · 2022Article
- Review
- Andrographolide Attenuates Blood-Brain Barrier Disruption, Neuronal Apoptosis, and Oxidative Stress Through Activation of Nrf2/HO-1 Signaling Pathway in Subarachnoid Hemorrhage.Neurotoxicity research · 2022Article
- Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke.Cellular and molecular neurobiology · 2022Review
- Differential Expression and Correlation Analysis of Global Transcriptome for Hemorrhagic Transformation After Acute Ischemic Stroke.Frontiers in neuroscience · 2022Article
- Scalp Electroacupuncture Promotes Angiogenesis after Stroke in Rats by Activation of Wnt/Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke.Molecular neurobiology · 2021Review
- Molecular Correlates of Hemorrhage and Edema Volumes Following Human Intracerebral Hemorrhage Implicate Inflammation, Autophagy, mRNA Splicing, and T Cell Receptor Signaling.Translational stroke research · 2021Article
- Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing.International journal of molecular sciences · 2021Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.
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