ArticleProceedings of the National Academy of Sciences of the United States of America2003
The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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
85 citing papers in PubMed, 197 citations in OpenAlex.
- CD103Nature communications · 2025Article
- Astrocytic PAR1 and mGluR2/3 control synaptic glutamate time course at hippocampal CA1 synapses.Glia · 2024Article
- Activated protein C in epilepsy pathophysiology.Frontiers in neuroscience · 2023Review
- Serum protease-activated receptor (PAR-1) levels as a potential biomarker for diagnosis of inflammation in type 2 diabetic patients.Inflammopharmacology · 2022Article
- Natural Killer Cells Are Present in Rag1Translational stroke research · 2022Article
- A GlutamateThe Journal of pharmacology and experimental therapeutics · 2021Article
- Article
- The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke.Translational stroke research · 2021Review
- The thrombin receptor links brain derived neurotrophic factor to neuron cholesterol production, resiliency and repair after spinal cord injury.Neurobiology of disease · 2021Article
- Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity.International journal of molecular sciences · 2021Review
- Ischemic stroke in PAR1 KO mice: Decreased brain plasmin and thrombin activity along with decreased infarct volume.PloS one · 2021Article
- CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke.Circulation research · 2020Article
- 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
- MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core.Scientific reports · 2018Article
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.Biological chemistry · 2018Article
- The impact of hypoxic-ischemic brain injury on stem cell mobilization, migration, adhesion, and proliferation.Neural regeneration research · 2018Review
- The Thrombin Receptor Restricts Subventricular Zone Neural Stem Cell Expansion and Differentiation.Scientific reports · 2018Article
- Astrocytes and the Warning Signs of Intracerebral Hemorrhagic Stroke.Neural plasticity · 2018Review
- Effect of oral tranexamic acid on macular edema associated with retinal vein occlusion or diabetes.Clinical ophthalmology (Auckland, N.Z.) · 2018Article
25 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
8 authors at 3 institutions in 1 country.
Funding
Abstract
The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown.
Indexed as
Identifiers
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.