ArticleStroke2015
Blood-brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke.
Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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
42 citing papers in PubMed, 70 citations in OpenAlex.
- Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial.Acta anaesthesiologica Scandinavica · 2022Trial
- LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.Stroke and vascular neurology · 2025Article
- Diversity of Brain Microvascular Endothelial Cell Functions: Physiology, Ischemia/Hypoxia, and Underlying Protection.Aging and disease · 2025Review
- IK Channel Confers Fine-tuning of Rod Bipolar Cell Excitation and Synaptic Transmission in the Retina.Function (Oxford, England) · 2025Article
- Integrating endothelium-derived hyperpolarization, nitric oxide, and prostacyclin pathways: the multimodal potential of human tissue kallikrein-1.Vascular biology (Bristol, England) · 2025Review
- The role of oxidative stress in blood-brain barrier disruption during ischemic stroke: Antioxidants in clinical trials.Biochemical pharmacology · 2024Review
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Alterations in brain fluid physiology during the early stages of development of ischaemic oedema.Fluids and barriers of the CNS · 2024Review
- Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones.Biomolecules · 2024Review
- Mechanisms of cerebrospinal fluid and brain interstitial fluid production.Neurobiology of disease · 2023Review
- 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
- Stroke-induced damage on the blood-brain barrier.Frontiers in neurology · 2023Review
- Impact of Electronic Cigarette Vaping on Cerebral Ischemia: What We Know So Far.Translational stroke research · 2022Review
- Effects of TRAM-34 and minocycline on neuroinflammation caused by diabetic ketoacidosis in a rat model.BMJ open diabetes research & care · 2022Article
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Effect of the KCa3.1 blocker, senicapoc, on cerebral edema and cardiovascular function after cardiac arrest - A randomized experimental rat study.Resuscitation plus · 2021Article
- Treatment with senicapoc in a porcine model of acute respiratory distress syndrome.Intensive care medicine experimental · 2021Article
- Cerebral Edema Formation After Stroke: Emphasis on Blood-Brain Barrier and the Lymphatic Drainage System of the Brain.Frontiers in cellular neuroscience · 2021Review
- Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke.Pharmaceutics · 2020Review
- Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeKCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na(+) and Cl(-) from the blood into the brain transcellularly through the co-operation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na(+) transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport.
methodsThe expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K(+) flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na(+) uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment.
resultsKCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na(+) uptake, and cytotoxic edema in the ischemic brain.
conclusionsBBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke.
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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.