Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
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Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.
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Both the glymphatic and the lymphatic systems eventually redirect proteins including sleep regulatory substances into lymph nodes and then into the circulation for final clearance by the liver or the kidneys.
“Both the glymphatic and the lymphatic systems eventually redirect proteins including sleep regulatory substances into lymph nodes and then into the circulation for final clearance by the liver or the kidneys”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [343]
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- Authors
- Louveau, A., Plog, B. A., Antila, S., Alitalo, K., Nedergaard, M., & Kipnis, J.
- Affiliations
- University of Virginia (US)
- University of Rochester Medicine (US)
- University of Helsinki (FI)
- University of Copenhagen (DK)
- Corresponding author
- Alitalo, Kari
- Nedergaard, Maiken
- Kipnis, Jonathan
- Venue
- Journal of Clinical Investigation
- Published
- 2017-09-01
- Volume
- 127
- Issue
- 9
- Pages
- 3210-3219
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5669566
- OpenAlex
- W2751474624
- Cited by
- 640
- References
- 107
- Citations by year
- 2026: 50 · 2025: 64 · 2024: 90 · 2023: 74 · 2022: 75 · 2021: 86 · 2020: 76 · 2019: 73 · 2018: 46 · 2017: 5
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- National Multiple Sclerosis Society
- Multiple Sclerosis Society
- Lundbeckfonden (R155-2016–552)
- Jane ja Aatos Erkon Säätiö
- Novo Nordisk Fonden (NNF13OC0004258)
- National Institutes of Health (AG034113)
- National Institute on Aging (R01AG048769, R01AG034113, R37AG034113)
- National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS096967, R01NS100366)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- glymphatic system, meningeal lymphatic vessels, cerebrospinal fluid, interstitial fluid, lymphatic drainage, meningeal immune cells, neurological disorders, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Central Nervous System, Central Nervous System Diseases, Dura Mater, Humans, Immune System, Lymph Nodes, Lymphatic System, Meninges, Neuroglia, Amyloid beta-Peptides, Lymphatic Vessels, Extracellular Fluid
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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.
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