ArticleThe Journal of general physiology2016
Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
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Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Pooled it
- High frame ratebioRxiv : the preprint server for biology · 2026Article
- Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.Pharmaceutical research · 2026Article
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Stretch and flow at the gliovascular interface: High-fidelity modeling of astrocyte endfeet.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Brief mechanical pulses induce sustained intracellular L-lactate production in astrocytes.Frontiers in cellular neuroscience · 2026Article
- Computational Fluid Dynamic Model Prediction of Enhanced Glymphatic Clearance in Response to Focused Ultrasound-Mediated Blood-Brain Barrier Opening.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Are diurnal variations in glymphatic clearance driven by circadian regulation of Aquaporin-4 expression?Fluids and barriers of the CNS · 2025Article
- Contrast Agent Clearance Dynamics and Diffusion in the Mouse Brain After Ventricular Administration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Brain fluid physiology in ischaemic stroke; more than just oedema.Fluids and barriers of the CNS · 2025Review
- Reply to: A curious concept of CNS clearance.Nature neuroscience · 2025Article
- Review
- Article
- Numerical simulation study of nanoparticle diffusion in gray matter.Computational and structural biotechnology journal · 2024Article
- Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries.Fluids and barriers of the CNS · 2024Article
- Regulation of brain fluid volumes and pressures: basic principles, intracranial hypertension, ventriculomegaly and hydrocephalus.Fluids and barriers of the CNS · 2024Review
- Brain clearance is reduced during sleep and anesthesia.Nature neuroscience · 2024Article
- The Association between Glymphatic System and Perivascular Macrophages in Brain Waste Clearance.Diagnostics (Basel, Switzerland) · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Image-guided subject-specific modeling of glymphatic transport and amyloid deposition.Computer methods in applied mechanics and engineering · 2023Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS.
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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.