ArticleCurrent neuropharmacology2014
Antagonists of the Vasopressin V1 Receptor and of the β(1)-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes - but the Mechanisms Differ.
Article in Current neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis.Molecular neurobiology · 2017Pooled it
- Zhenwu Decoction Attenuates Water-Retention-Related Phenotypes and Multiorgan Injury in Rats With Doxorubicin-Induced Chronic Heart Failure.Cardiovascular therapeutics · 2026Article
- Neutrophil βBritish journal of pharmacology · 2023Article
- The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review.International journal of molecular sciences · 2023Review
- Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials.Frontiers in stroke · 2023Review
- Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Review
- Blockade of Arginine Vasopressin receptors prevents blood-brain barrier breakdown in Experimental Autoimmune Encephalomyelitis.Scientific reports · 2020Article
- The Astrocytic cAMP Pathway in Health and Disease.International journal of molecular sciences · 2019Review
- Involvement of Epigenetic Mechanisms and Non-coding RNAs in Blood-Brain Barrier and Neurovascular Unit Injury and Recovery After Stroke.Frontiers in neuroscience · 2019Review
- The Dual Role of AQP4 in Cytotoxic and Vasogenic Edema Following Spinal Cord Contusion and Its Possible Association With Energy Metabolism via COX5A.Frontiers in neuroscience · 2019Article
- Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target Intervention.Journal of molecular neuroscience : MN · 2018Review
- Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation.Frontiers in cellular neuroscience · 2016Review
- Role of the Astrocytic Na(+), K(+)-ATPase in K(+) Homeostasis in Brain: K(+) Uptake, Signaling Pathways and Substrate Utilization.Neurochemical research · 2015Review
- Malignant MCA Stroke: an Update on Surgical Decompression and Future Directions.Current atherosclerosis reports · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain edema is a serious complication in ischemic stroke because even relatively small changes in brain volume can compromise cerebral blood flow or result in compression of vital brain structures on account of the fixed volume of the rigid skull. Literature data indicate that administration of either antagonists of the V1 vasopressin (AVP) receptor or the β1-adrenergic receptor are able to reduce edema or infarct size when administered after the onset of ischemia, a key advantage for possible clinical use. The present review discusses possible mechanisms, focusing on the role of NKCC1, an astrocytic cotransporter of Na(+), K(+), 2Cl(-) and water and its activation by highly increased extracellular K(+) concentrations in the development of cytotoxic cell swelling. However, it also mentions that due to a 3/2 ratio between Na(+) release and K(+) uptake by the Na(+),K(+)-ATPase driving NKCC1 brain extracellular fluid can become hypertonic, which may facilitate water entry across the blood-brain barrier, essential for development of edema. It shows that brain edema does not develop until during reperfusion, which can be explained by lack of metabolic energy during ischemia. V1 antagonists are likely to protect against cytotoxic edema formation by inhibiting AVP enhancement of NKCC1-mediated uptake of ions and water, whereas β1-adrenergic antagonists prevent edema formation because β1-adrenergic stimulation alone is responsible for stimulation of the Na(+),K(+)-ATPase driving NKCC1, first and foremost due to decrease in extracellular Ca(2+) concentration. Inhibition of NKCC1 also has adverse effects, e.g. on memory and the treatment should probably be of shortest possible duration.
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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.