ReviewJournal of neurosurgery2010
Molecular mechanisms of microvascular failure in central nervous system injury--synergistic roles of NKCC1 and SUR1/TRPM4.
Review in Journal of neurosurgery, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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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
80 citing papers in PubMed, 143 citations in OpenAlex.
- A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury.Journal of neurosurgery · 2013Trial
- Article
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Ion Channel Dysregulation Following Intracerebral Hemorrhage.Neuroscience bulletin · 2024Review
- Genetic and molecular mechanisms of hydrocephalus.Frontiers in molecular neuroscience · 2024Review
- A machine learning model based on results of a comprehensive radiological evaluation can predict the prognosis of basal ganglia cerebral hemorrhage treated with neuroendoscopy.Frontiers in neurology · 2024Article
- Predictors of mortality at 3 months in patients with skull base tumor resections in a low-income setting.Frontiers in surgery · 2024Article
- A machine learning approach for predicting perihematomal edema expansion in patients with intracerebral hemorrhage.European radiology · 2023Article
- TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion.Biomedicines · 2023Article
- Intravenous Injection of Na Ions Aggravates Ang II-Induced Hypertension-Related Vascular Endothelial Injury by Increasing Transmembrane Osmotic Pressure.International journal of nanomedicine · 2023Article
- Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Are GABAergic drugs beneficial in providing neuroprotection after traumatic brain injuries? A comprehensive literature review of preclinical studies.Frontiers in neurology · 2023Review
- Binding epitope for recognition of human TRPM4 channel by monoclonal antibody M4M.Scientific reports · 2022Article
- Article
- Variants in genes encoding the SUR1-TRPM4 non-selective cation channel and sudden infant death syndrome (SIDS): potentially increased risk for cerebral edema.International journal of legal medicine · 2022Article
- Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke.Cellular and molecular neurobiology · 2022Review
- Defining Delayed Perihematomal Edema Expansion in Intracerebral Hemorrhage: Segmentation, Time Course, Risk Factors and Clinical Outcome.Frontiers in immunology · 2022Article
- Lack of NHE6 and Inhibition of NKCC1 Associated With Increased Permeability in Blood Labyrinth Barrier-Derived Endothelial Cell Layer.Frontiers in cellular neuroscience · 2022Article
- Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel-Part 2: TRPM4 in Health and Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
20 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Microvascular failure largely underlies the damaging secondary events that accompany traumatic brain injury (TBI). Changes in capillary permeability result in the extravasation of extracellular fluid, inflammatory cells, and blood, thereby producing cerebral edema, inflammation, and progressive secondary hemorrhage (PSH). Recent work in rat models of TBI and stroke have implicated 2 ion transport proteins expressed in brain endothelial cells as critical mediators of edema formation: the constitutively expressed Na(+)-K(+)-2Cl(-) cotransporter, NKCC1, and the trauma/ischemia-induced SUR1-regulated NC(Ca-ATP) (SUR1/TRPM4) channel. Whereas NKCC1 function requires adenosine 5'-triphosphate (ATP), activation of SUR1/TRPM4 occurs only after ATP depletion. This opposite dependence on intracellular ATP levels implies that one or the other mechanism will activate/deactivate as ATP concentrations rise and fall during periods of ischemia/reperfusion, resulting in continuous edema formation regardless of cellular energy status. Moreover, with critical ATP depletion, sustained opening of SUR1/TRPM4 channels results in the oncotic death of endothelial cells, leading to capillary fragmentation and PSH. Bumetanide and glibenclamide are 2 well-characterized, safe, FDA-approved drugs that inhibit NKCC1 and the SUR1/TRPM4 channel, respectively. When used alone, these drugs have provided documented beneficial effects in animal models of TBI- and ischemiaassociated cerebral edema and PSH. Given the mechanistic and temporal differences by which NKCC1 and the SUR1/TRPM4 channel contribute to the pathophysiological mechanisms of these events, combination therapy with bumetanide and glibenclamide may yield critical synergy in preventing injury-associated capillary failure.
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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.