The Brain’s Glymphatic System: Current Controversies
Open accessAbstract
The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the central nervous system (CNS). Imaging studies, as well as manipulations of fluid transport, point to a key role of the glymphatic-lymphatic system in clearance of amyloid-β and other proteins. As such, the glymphatic-lymphatic system represents a new target in combating neurodegenerative diseases. Not unexpectedly, introduction of a new plumbing system in the brain has stirred controversies. This opinion article will highlight what we know about the brain's fluid transport systems, where experimental data are lacking, and what is still debated.
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Glymphatic fluid transport is directionally polarized: influx along penetrating arteries, AQP4-supported entry into neuropil, and efflux along peri-venous spaces and cranial and spinal nerves.
“fluid transport through the glymphatic system is directionally polarized, with influx along penetrating arteries, fluid entry into the neuropil supported by AQP4, and efflux along the peri-venous spaces, as well as along the cranial and spinal nerves (24, 32–34).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [34]
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“of reactive oxygen species (molecular level), regulation of neurogenesis, synapse formation, maintenance and elimination (cellular and network levels), regulation of blood flow, glycogen synthesis and storage (metabolic level), as well as control of the BBB and glymphatic clearance (whole brain level) (Hanisch and Ket…”
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- Authors
- Mestre, H., Mori, Y., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- University of Copenhagen (DK)
- Corresponding author
- Nedergaard, Maiken
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 43
- Issue
- 7
- Pages
- 458-466
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC7331945
- OpenAlex
- W3025374083
- Cited by
- 609
- References
- 71
- Citations by year
- 2026: 83 · 2025: 123 · 2024: 97 · 2023: 88 · 2022: 109 · 2021: 87 · 2020: 19 · 2015: 1
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Neurosciences (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01NS100366, RF1AG057575)
- Novo Nordisk
- National Institute of Neurological Disorders and Stroke
- Horizon 2020 (666881)
- Army Research Office (MURI W911NF1910280)
- Government of South Australia
- National Institutes of Health
- Lundbeckfonden
- Fondation Leducq
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- glymphatic system, meningeal lymphatic vessels, cerebrospinal fluid transport, amyloid-beta clearance, neurodegenerative diseases
- MeSH terms
- Glymphatic System, Brain, Central Nervous System, Humans, Neurodegenerative Diseases, Lymphatic Vessels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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