ArticleeLife2023
Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses that pooled it.
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
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Clinical and preclinical evidence of meningeal immunity and glymphatic pathways in stroke: a systematic review.Frontiers in immunology · 2026Pooled it
- Unveiling the glymphatic system's impact on neurodegenerative diseases: a comprehensive bibliometric analysis (2012-2024).Frontiers in aging neuroscience · 2025Pooled it
- Glymphatic function in humans: indicators, modulators, and measurement strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Integrated Transcriptomic Analysis Reveals Coordinated Gliovascular Remodeling Across Diffuse Glioma Grades.Cancers · 2026Article
- Central nervous system lymphatic network: from the maintenance of brain homeostasis to emerging therapeutic perspectives in neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Glymphatic dysfunction in cerebellar neurodegeneration: mechanistic insights and emerging clinical implications.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Chronic Smoking Impairs Glymphatic Transport and Cognitive Function in Adolescent Mice Through Cardiac, Vascular, and Perivascular Aquaporin-4 Mechanisms.CNS neuroscience & therapeutics · 2026Article
- Review
- Early glymphatic failure in AppNL-F knock-in mice is linked to parenchymal border macrophages loss.Brain : a journal of neurology · 2026Article
- Divergent Glymphatic Dysfunction and Free Water Pathology Underpin Distinct Mechanisms and Enable Differential Diagnosis in Parkinson's Disease and Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Putative glymphatic function and free water in schizophrenia: A 7T DTI study across psychosis stages.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Glutamate carboxypeptidase II activation in astrocytes mediates glymphatic impairment and cognitive vulnerability in the aging brain following surgery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Aging macaques bridge the translational gap in perivascular space biology.Scientific reports · 2026Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Influence of an AQP4 haplotype and sleep duration on early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- MR-AIV reveals in vivo brain-wide fluid flow with physics-informed AI.Science advances · 2026Article
- The glymphatic system and glioblastoma.Brain : a journal of neurology · 2026Review
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
55 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
11 authors at 2 institutions in 4 countries.
Funding
Abstract
The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular endfeet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport. Yet, no studies have systematically examined how these abnormalities in structure and water transport correlate with glymphatic function. Here, we used high-resolution 3D magnetic resonance (MR) non-contrast cisternography, diffusion-weighted MR imaging (MR-DWI) along with intravoxel-incoherent motion (IVIM) DWI, while evaluating glymphatic function using a standard dynamic contrast-enhanced MR imaging to better understand how water transport and glymphatic function is disrupted after genetic deletion of AQP4. AQP4 KO mice had larger interstitial spaces and total brain volumes resulting in higher water content and reduced CSF space volumes, despite similar CSF production rates and vascular density compared to wildtype mice. The larger interstitial fluid volume likely resulted in increased slow but not fast MR diffusion measures and coincided with reduced glymphatic influx. This markedly altered brain fluid transport in AQP4 KO mice may result from a reduction in glymphatic clearance, leading to enlargement and stagnation of fluid in the interstitial space. Overall, diffusion MR is a useful tool to evaluate glymphatic function and may serve as valuable translational biomarker to study glymphatics in human disease.
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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.