ArticleStroke2013
Role of SCH79797 in maintaining vascular integrity in rat model of subarachnoid hemorrhage.
Article in Stroke, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- PAK1 inhibition synergistically enhances the anti-tumor efficacy of PARP inhibitors in ovarian cancers.Genes & diseases · 2026Article
- Acupuncture modulates actin homeostasis and promotes myelin sheath regeneration in rat models of intracerebral hemorrhage.Journal of molecular histology · 2026Article
- GlialeLife · 2026Article
- Association between serum calcium level and the risk of acute kidney injury in ICU patients with subarachnoid hemorrhage: a retrospective cohort study.Frontiers in neurology · 2024Article
- miR-18a-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates early brain injury following subarachnoid hemorrhage through blockade of the ENC1/p62 axis.Cell and tissue research · 2023Article
- PLPP/CIN-mediated NF2 S10 dephosphorylation distinctly regulates kainate-induced seizure susceptibility and neuronal death through PAK1-NF-κB-COX-2-PTGES2 signaling pathway.Journal of neuroinflammation · 2023Article
- Metformin Preserves VE-Cadherin in Choroid Plexus and Attenuates Hydrocephalus via VEGF/VEGFR2/p-Src in an Intraventricular Hemorrhage Rat Model.International journal of molecular sciences · 2022Article
- The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke.Translational stroke research · 2021Review
- Protease-Activated Receptor-1 Antagonist Protects Against Lung Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2021Article
- Podocyte Integrin-Journal of the American Society of Nephrology : JASN · 2020Article
- Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis.Frontiers in pharmacology · 2020Article
- Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia/Reperfusion Injury.Neural plasticity · 2020Article
- Thrombin disrupts vascular endothelial-cadherin and leads to hydrocephalus via protease-activated receptors-1 pathway.CNS neuroscience & therapeutics · 2019Article
- Tristetraprolin attenuates brain edema in a rat model of cerebral hemorrhage.Brain and behavior · 2019Article
- Weisheng-Tang Ameliorates Acute Ischemic Brain Damage in Mice by Maintaining Blood-Brain Barrier Integrity.Oxidative medicine and cellular longevity · 2019Article
- Thrombin contributes to the injury development and neurological deficit after acute subdural hemorrhage in rats only in collaboration with additional blood-derived factors.BMC neuroscience · 2018Article
- Subarachnoid hemorrhage enhances the expression of TDP-43 in the brain of experimental rats and human subjects.Experimental and therapeutic medicine · 2018Article
- Neuroprotective Effect of Protein Phosphatase 2A/Tristetraprolin Following Subarachnoid Hemorrhage in Rats.Frontiers in neuroscience · 2018Article
- Targeting PAR1: Now What?Trends in pharmacological sciences · 2017Review
- Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke.Neural plasticity · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposePlasma thrombin concentration is increased after subarachnoid hemorrhage (SAH). However, the role of thrombin receptor (protease-activated receptor-1 [PAR-1]) in endothelial barrier disruption has not been studied. The aims of this study were to investigate the role of PAR-1 in orchestrating vascular permeability and to assess the potential therapeutics of a PAR-1 antagonist, SCH79797, through maintaining vascular integrity.
methodsSCH79797 was injected intraperitoneally into male Sprauge-Dawley rats undergoing SAH by endovascular perforation. Assessment was conducted at 24 hours after SAH for brain water content, Evans blue content, and neurobehavioral testing. To explore the role of PAR-1 activation and the specific mechanism of SCH79797's effect after SAH, Western blot, immunoprecipitation, and immunofluorescence of hippocampus tissue were performed. A p21-activated kinase-1 (PAK1) inhibitor, IPA-3, was used to explore the underlying protective mechanism of SCH79797.
resultsAt 24 hours after SAH, animals treated with SCH79797 demonstrated a reduction in brain water content, Evans blue content, and neurobehavioral deficits. SCH79797 also attenuated PAR-1 expression and maintained the level of vascular endothelial-cadherin, an important component of adherens junctions. Downstream to PAR-1, c-Src-dependent activation of p21-activated kinase-1 led to an increased serine/threonine phosphorylation of vascular endothelial-cadherin; immunoprecipitation results revealed an enhanced binding of phosphorylated vascular endothelial-cadherin with endocytosis orchestrator β-arrestin-2. These pathological states were suppressed after SCH79797 treatment.
conclusionsPAR-1 activation after SAH increases microvascular permeability, at least, partly through a PAR-1-c-Src-p21-activated kinase-1-vascular endothelial-cadherin phosphorylation pathway. Through suppressing PAR-1 activity, SCH79797 plays a protective role in maintaining microvascular integrity after SAH.
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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.