ReviewNeuron2025
Resolving the mysteries of brain clearance and immune surveillance.
Abstract readReview
In one paragraph
Review in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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
32 citing papers in PubMed.
- Spatial organization of AQP4 water channel expression in the human brain.Science advances · 2026Article
- Brain clearance physiology in traumatic brain injury: From disruption to therapeutic potential.The Journal of physiology · 2026Article
- In-silico solute transport via perivascular networks in the human intracranial space.Nature communications · 2026Article
- Leptomeningeal fibroblasts promote glioblastoma progression by regulating cerebrospinal fluid dynamics.Nature communications · 2026Article
- HD-tDCS Restores Perivascular AQP4 Polarization via PPARγ Modulation to Enhance Glymphatic Clearance After Intracerebral Hemorrhage in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regional wasteosome accumulation across neurodegenerative diseases points to a shared underlying mechanism potentially related to glymphatic insufficiency.Acta neuropathologica communications · 2026Article
- Author's reply to "POTS: A neuroimmune disorder with cardiovascular manifestations".Heart rhythm O2 · 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
- Ventricular CSF-to-blood water transport kinetics in adult hydrocephalus.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Estimation of human brain fluid clearance using intrathecal imaging contrast agents.Fluids and barriers of the CNS · 2026Observational
- Postmortem Evidence of Lymphatic Vessels Located at the Boundary of Central and Peripheral Nervous Systems in the Cervical Spine.Cellular and molecular neurobiology · 2026Article
- microGLYMPH: a conceptual translational roadmap for microdialysis‑based assessment of CSF-interstitial solute exchange in acquired brain injury.Critical care (London, England) · 2026Review
- Quantitative assessment of flow between cerebrospinal and interstitial fluid compartments in humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Developmental changes in diffusion MRI metrics along the perivascular space in children during the first 5 years of life.Pediatric radiology · 2026Article
- Glymphatic dysfunction: a unifying hypothesis for delirium.Nature reviews. Neurology · 2026Review
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.MedComm · 2026Review
- The Effect of Cranio-Cervical Artery Stenosis on Glymphatic System Function in Patients with Cerebral Infarction.Journal of clinical medicine · 2026Article
- Coupling between global brain blood oxygen level-dependent activity and cerebrospinal fluid dynamics in young endurance athletes.Experimental physiology · 2026Article
- Surrogates of glymphatic metrics decline and coupled sleep rhythms disruption in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Jonathan KipnisCenter for Brain Immunology and Glia (BIG), Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: kipnis@wustl.edu.
Helene BenvenisteDepartment of Anesthesiology and Department of Biomedical Engineering, Yale School of Medicine, New Haven, CT, USA.
Anne EichmannCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06511, USA; Paris Cardiovascular Research Center, Inserm U970, Université Paris, Paris, France.
Jean-Leon ThomasDepartment of Neurology, Yale University School of Medicine, New Haven, CT, USA; Paris Brain Institute, Université Pierre et Marie Curie Paris 06, Inserm UMRS1127, Sorbonne Université, Paris, France.
Daniel S ReichTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Laura D LewisDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
Li-Huei TsaiPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Antoine DrieuUniversité Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Paris, France.
Erik N T P BakkerAmsterdam UMC location University of Amsterdam, Biomedical Engineering and Physics, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Microcirculation, Amsterdam, the Netherlands; Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, the Netherlands.
Douglas H KelleyDepartment of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA.
Iben LundgaardDepartment of Experimental Medical Science, Lund University, Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Humberto MestreDivision of Neurocritical Care, Department of Neurology, Massachusetts General Brigham, Harvard Medical School, Boston, MA, USA.
Benedikt ZottInstitute of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany; Institute of Neuroscience, Technical University of Munich, Munich, Germany.
Per Kristian EideDepartment of Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for Brain Fluid Research, University of Oslo, Oslo, Norway.
Matthias J P van OschC.J. Gorter MRI Center, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Susanne J van VeluwBHF-UK DRI Centre for Vascular Dementia Research, University of Edinburgh, Edinburgh, Scotland; Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, Scotland.
Jeffrey IliffVISN 20 Northwest Mental Illness Research, Education and Clinical Center, VA Puget Sound Healthcare System, Seattle, WA, USA; Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
Andrew C YangGladstone Institute of Neurological Disease, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Laura SantambrogioEnglander Institute of Precision Medicine, Department of Biochemistry and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA.
Sandro Da MesquitaDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Richard DanemanDepartments of Pharmacology and Neurosciences, University of California, 9500 Gilman Dr., BSB3090, San Diego, CA 92093, USA.
Justin RustenhovenDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand; Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Steven A GoldmanCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14580, USA; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen N 2200, Denmark.
Maiken NedergaardCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14580, USA; Center for Translational Neuromedicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen N 2200, Denmark. Electronic address: nedergaard@urmc.rochester.edu.
Funding
Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectorsU19NS128613 · NINDS · UNIVERSITY OF ROCHESTER · PI Laura Diane Lewis · 2022 to 2026
$13.6MVascular-immune mechanisms of cerebral amyloid angiopathy and Alzheimer's pathologyRF1NS139975 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI ARFANAKIS, KONSTANTINOS, BLURTON-JONES, MATHEW MARK · 2024 to 2024
$5.4MNeuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiologyR01AT011429 · NCCIH · MASSACHUSETTS GENERAL HOSPITAL · PI Laura Diane Lewis · 2021 to 2026
$3.7MRobust workflow software for MRI tracking of glymphatic-lymphatic couplingR01AT011419 · NCCIH · YALE UNIVERSITY · PI BENVENISTE, HELENE D, KIPNIS, JONATHAN · 2021 to 2025
$3.6MSleep-dependent modulation of cerebrospinal fluid flow in aging and across genetic risk for Alzheimers diseaseR01AG070135 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEWIS, LAURA DIANE · 2021 to 2025
$3.3MThe glymphatic system at the crossroad of integrative health approaches inchronic painR01AT011439 · NCCIH · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2021 to 2025
$3.1MNoninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s DiseaseR01AT011460 · NCCIH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2021 to 2025
$3.0MManipulating Neural Oscillations with Non-Invasive Sensory Stimulation for Alzheimer's Disease InterventionR01AG069232 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2022 to 2025
$2.8MChronic Alcohol, Dementia, and CNS Fluid HomeostasisR01AA030183 · NIAAA · YALE UNIVERSITY · PI Helene D Benveniste, Graeme F Mason · 2022 to 2026
$2.5MRole of Sleep Disruption after mTBI as a Driver of Chronic Post-traumatic HeadacheR01NS129573 · NINDS · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI Jeffrey J Iliff, Andrew F Russo · 2023 to 2026
$2.4MRole of apoE-mediated meningeal lymphatic remodeling in the pathophysiology of Alzheimer’s diseaseRF1AG080556 · NIA · MAYO CLINIC JACKSONVILLE · PI DA MESQUITA, SANDRO · 2023 to 2023
$2.3MLymphatic drainage dysfunction in chronic hypertensionR01HL176017 · NHLBI · YALE UNIVERSITY · PI Helene D Benveniste, Anne Christine Eichmann · 2024 to 2026
$2.2MNCCIH NIH HHS R01 AT011419NCCIH NIH HHS R01 AT011429NCCIH NIH HHS R01 AT011439NCCIH NIH HHS R01 AT011460NCCIH NIH HHS R01 AT012312NHLBI NIH HHS R01 HL176017NIAAA NIH HHS R01 AA030183NIA NIH HHS R01 AG069232NIA NIH HHS R01 AG070135NIA NIH HHS RF1 AG080556NINDS NIH HHS R01 NS129573NINDS NIH HHS R01 NS130057NINDS NIH HHS RF1 NS139975NINDS NIH HHS U19 NS128613
Abstract
Recent advances are transforming our understanding of brain fluid dynamics, highlighting cerebrospinal fluid (CSF) flow as a key process in brain waste clearance. While debates persist regarding its anatomical pathways and regulatory mechanisms, certain core principles have become widely accepted. CSF influx occurs primarily along periarterial spaces, solute clearance follows multiple routes, and glymphatic and meningeal lymphatic systems are functionally connected. Brain clearance is influenced by vascular pulsation, neural activity, and sleep. Immune cells at brain-border niches both monitor solute efflux and modulate flow, linking brain clearance to neuroimmune interactions. A deeper understanding of brain clearance could unlock new therapeutic avenues for autoimmune, neurodegenerative, neoplastic, and psychiatric disorders.
Indexed as
BrainCerebrospinal FluidImmunologic SurveillanceAnimalsGlymphatic SystemHumansCSF drainageglymphaticsimmune surveillancemeningeal lymphaticsmeningesneuroimmunology
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC
Read underepoch 390
Registered trials
None linked
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.