ArticleStroke2008
Synergistic effect of an endothelin type A receptor antagonist, S-0139, with rtPA on the neuroprotection after embolic stroke.
Article in Stroke, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.Neurocritical care · 2024Article
- Sovateltide Mediated Endothelin B Receptors Agonism and Curbing Neurological Disorders.International journal of molecular sciences · 2022Review
- The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Novel Targets and Interventions for Cognitive Complications of Diabetes.Frontiers in physiology · 2021Review
- Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro.Canadian journal of physiology and pharmacology · 2020Article
- Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions.Canadian journal of physiology and pharmacology · 2020Article
- Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke.Stroke · 2019Article
- Treatment of acute cerebral ischemia using animal models: a meta-analysis.Translational neuroscience · 2015Review
- Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia.PloS one · 2014Article
- Normobaric hyperoxia combined with minocycline provides greater neuroprotection than either alone in transient focal cerebral ischemia.Experimental neurology · 2013Article
- The effect of endothelin receptor A antagonism on basilar artery endothelium-dependent relaxation after ischemic stroke.Life sciences · 2012Article
- Neurological deficits in mice with profound biotinidase deficiency are associated with demylination and axonal degeneration.Neurobiology of disease · 2012Article
- Impact of tissue plasminogen activator on the neurovascular unit: from clinical data to experimental evidence.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2011Review
- Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.Biological research for nursing · 2011Article
- Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes.Canadian journal of physiology and pharmacology · 2010Article
- Article
- Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disorders.Journal of neurochemistry · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeUsing a model of embolic stroke, the present study tested the hypothesis that blockage of endothelin-1 with S-0139, a specific endothelin type A receptor (ET(A)) antagonist, enhances the neuroprotective effect of recombinant tissue plasminogen activator (rtPA) by suppressing molecules that mediate thrombosis and blood brain barrier (BBB) disruption induced by ischemia and rtPA.
methodsRats (n=104) subjected to embolic middle cerebral artery (MCA) occlusion were randomly divided into 1 of 4 infusion groups with 26 rats per group: (1) the control group in which rats were administered saline, (2) the monotherapy rtPA group in which rtPA was intravenously administered at a dose of 10 mg/kg 4 hours after MCA occlusion, (3) the monotherapy S-0139 group in which S-0139 was intravenously given 2 hours after MCA occlusion, and (4) the combination of rtPA +S-0139 group in which S-0139 and rtPA were given 2 and 4 hours after MCA occlusion, respectively. Measurements of infarct volume and parenchymal hemorrhage, behavioral outcome, and immunostaining were performed on rats euthanized 1 and 7 days after stroke.
resultsThe combination therapy of S-0139 and rtPA significantly (P<0.01) reduced infarct volume (24.8+/-0.9% versus 33.8+/-1.5% in control) and hemorrhagic area (7.1+/-6.1 microm(2) versus 36.5+/-19.2 microm(2) in control) and improved functional recovery compared with control saline-treated animals. Immunostaining analysis revealed that the combination therapy had the synergistically suppressed ischemia- and rtPA-induced ICAM-1, protease-activated receptor 1 (PAR-1), as well as accumulation of platelets in cerebral microvessels. Furthermore, the combination treatment synergistically reduced loss of laminin, ZO1, and occludin in cerebral vessels.
conclusionsThese data suggest that S-0139 provides the neuroprotection by suppressing ischemia- and rtPA-triggered molecules that evoke thrombosis and BBB disruption.
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.