ArticleCell2020
Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 301 papers, 1 of them a synthesis that pooled it.
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
301 citing papers in PubMed, 1 synthesis or guideline pooled it, 421 citations in OpenAlex.
- The Role of Aquaporins in Epileptogenesis-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Ultrasound-Responsive Piezoelectric Fibrous Membrane Promotes Neurological Recovery After TBI by Modulating Microglial Polarization via Restoring Mitochondrial Dynamic Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model.bioRxiv : the preprint server for biology · 2026Article
- Varicose projection astrocytes: Conserved reactive cells in brain pathology.Science advances · 2026Article
- Model of ocular surface ion and water transport predicts efficacy of dry eye therapeutics.The Journal of general physiology · 2026Article
- Variations of Corticotropin-Releasing Factor Receptor 1α Contribute to the Blunted HPA Axis Responses to Hypoxia in Plateau Mammals.Neuroscience bulletin · 2026Article
- Experimental models of cerebral small vessel disease: Physiological constraints, translational challenges and future directions.The Journal of physiology · 2026Review
- ROS-Responsive Trifluoperazine Prodrug Nanoparticles and Mesenchymal Stem Cell Exosomes Synergistically Modulate Astrocyte Phenotype for Spinal Cord Injury Repair.ACS applied materials & interfaces · 2026Article
- Spinal Cord Ischemia Following Thoracoabdominal Aortic Aneurysm Repair: Translational Insights from Stroke and Traumatic Injury for Biomarker Development.Biomedicines · 2026Review
- Exploring the Therapeutic Potential of Aquaporin-4 Modulation in Sepsis: Inhibitors and Facilitators.International journal of molecular sciences · 2026Article
- LRBA organizes distinct vesicular trafficking systems in distal nephron segments for water and sodium conservation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis.Science advances · 2026Article
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Adenosine AJournal of neurochemistry · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Canine Cognitive Dysfunction and Alzheimer's Disease: Pathophysiological Relationships and the Impact of Glymphatic System Impairment on Neurodegeneration.Veterinary sciences · 2026Review
- Astrocytes: Unveiling their role in the molecular mechanism of natural antidepressants.Journal of pharmaceutical analysis · 2026Review
- Repeated moderate hypothermia leads to sustained glymphatic dysfunction and loss of vascular AQP4 polarization.Fluids and barriers of the CNS · 2026Article
241 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 7 countries.
Funding
Abstract
Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
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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.