ReviewFrontiers in neurology2021
Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis.
Review in Frontiers in neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 62 citations in OpenAlex.
- Managing hyponatremia: fast or slow? Why, when, how, and controversies.Clinical kidney journal · 2026Review
- Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.Psychopharmacology · 2026Review
- Novel Therapeutic Insights Into Alzheimer's Disease: Glymphatic System and Meningeal Lymphatic Vessels.Aging cell · 2026Review
- Astrocyte-Microglia Crosstalk in Post-Hemorrhagic Neurovascular Microenvironment: Mechanistic Nodes, Cross-Stroke Comparisons, and Therapeutic Reprogramming.Translational stroke research · 2026Review
- Yin Yang 1 Specifically Supports the Development of Olig2 Positive Cerebellar Astrocytes.Glia · 2026Article
- Glymphatic Dysfunction and Aquaporin-4 Dysregulation in Traumatic Brain Injury and Brain Tumors: A Review.Molecular neurobiology · 2026Review
- The Glymphatic System and Neurosurgery: A Comprehensive Narrative Review of Current Concepts and Future Directions.Journal of clinical medicine · 2026Review
- The electrofluidic brain as a basement layer for neural computation.Communications biology · 2026Review
- Evidence for direct and sleep-moderated relationships between aquaporin-4 genetic variants and Alzheimer's disease phenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- DTI-ALPS Is Associated with Temporolimbic Amyloid but Not Plasma p-Tau181 Across the Alzheimer's Disease Continuum.Research square · 2026Article
- Neurovascular Coupling Disruption and Glymphatic Dysfunction Are Associated With Visual Impairment in Pediatric Monocular Anisometropic Amblyopia.Investigative ophthalmology & visual science · 2026Article
- The Protective Role of Aquaporin 4 (AQP4) in Temporal Lobe Epilepsy: Yes or No?Journal of molecular neuroscience : MN · 2026Review
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- AI-Resolved Protein Energy Landscapes, Electrodynamics, and Fluidic Microcircuits as a Unified Framework for Predicting Neurodegeneration.International journal of molecular sciences · 2026Review
- Post-stroke glymphatic and meningeal lymphatic dysfunction: mechanisms, imaging evidence, and translational challenges.Frontiers in stroke · 2026Review
- The postictal systems window hypothesis of electroconvulsive therapy in major depression.Frontiers in psychiatry · 2026Article
- Variability in the circulation of cerebrospinal fluid: causes and clinical implications for intraventricular drug delivery.Frontiers in drug delivery · 2026Review
- Free water-mediated associations among choroid plexus enlargement, white matter lesions, and cognitive performance in type 2 diabetes mellitus.Frontiers in endocrinology · 2026Article
- Role of AQP4 in ameliorating heat stress-induced cellular injury in a cell line model through active heat acclimation.Frontiers in human neuroscience · 2026Article
- Autism Spectrum Disorder and Perivascular Spaces: An Integrative Perspective Across the Lifespan.Journal of clinical medicine · 2025Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the past, water homeostasis of the brain was understood as a certain quantitative equilibrium of water content between intravascular, interstitial, and intracellular spaces governed mostly by hydrostatic effects i.e., strictly by physical laws. The recent achievements in molecular bioscience have led to substantial changes in this regard. Some new concepts elaborate the idea that all compartments involved in cerebral fluid homeostasis create a functional continuum with an active and precise regulation of fluid exchange between them rather than only serving as separate fluid receptacles with mere passive diffusion mechanisms, based on hydrostatic pressure. According to these concepts, aquaporin-4 (AQP4) plays the central role in cerebral fluid homeostasis, acting as a water channel protein. The AQP4 not only enables water permeability through the blood-brain barrier but also regulates water exchange between perivascular spaces and the rest of the glymphatic system, described as pan-cerebral fluid pathway interlacing macroscopic cerebrospinal fluid (CSF) spaces with the interstitial fluid of brain tissue. With regards to this, AQP4 makes water shift strongly dependent on active processes including changes in cerebral microcirculation and autoregulation of brain vessels capacity. In this paper, the role of the AQP4 as the gatekeeper, regulating the water exchange between intracellular space, glymphatic system (including the so-called neurovascular units), and intravascular compartment is reviewed. In addition, the new concepts of brain edema as a misbalance in water homeostasis are critically appraised based on the newly described role of AQP4 for fluid permeation. Finally, the relevance of these hypotheses for clinical conditions (including brain trauma and stroke) and for both new and old therapy concepts are analyzed.
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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 Socratic graph.