ArticleGlia2024
Glymphatic fluid transport is suppressed by the aquaporin-4 inhibitor AER-271.
Article in Glia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 21 citations in OpenAlex.
- Multimodal imaging maps spinal glymphatic transport in health and its disruption after injury.bioRxiv : the preprint server for biology · 2026Article
- High frame ratebioRxiv : the preprint server for biology · 2026Article
- Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.Psychopharmacology · 2026Review
- 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
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.MedComm · 2026Review
- How is rosette formation in brain tumours linked with cerebrospinal fluid spread?Brain tumor pathology · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Network mechanisms of glymphatic system dysfunction in the disruption of the "brain-lung axis".Frontiers in neurology · 2026Review
- Review
- Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke.Brain pathology (Zurich, Switzerland) · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.Biomedicines · 2025Review
- Relationships between measures of neurovascular integrity and fluid transport in aging: a multi-modal neuroimaging study.Fluids and barriers of the CNS · 2025Article
- Diffusion Tensor Imaging in Neurofluids.Neuroimaging clinics of North America · 2025Review
- Glymphatic system dysfunction and cerebrospinal fluid retention in gliomas: evidence from perivascular space diffusion and volumetric analysis.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Aquaporin-4 in glioblastoma: a nexus of glymphatic dysfunction, edema, immune evasion, and treatment resistance.Frontiers in cellular neuroscience · 2025Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin-4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER-271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER-271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion-weighted MRI. Furthermore, AER-271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER-271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild-type but not in AQP4 deficient mice, we foresee AER-271 as a new tool for manipulation of the glymphatic system in rodent brain.
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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.