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Cited by 254Cerebrospinal fluid and hydrocephalusBarrier Structure and Function StudiesIon Transport and Channel Regulation

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The glymphatic system: implications for drugs for central nervous system diseases

Lohela, Terhi J., Lilius, Tuomas O., Nedergaard, Maiken·2022·Nature Reviews Drug Discovery
DOI 10.1038/s41573-022-00500-9
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Abstract

In the past decade, evidence for a fluid clearance pathway in the central nervous system known as the glymphatic system has grown. According to the glymphatic system concept, cerebrospinal fluid flows directionally through the brain and non-selectively clears the interstitium of metabolic waste. Importantly, the glymphatic system may be modulated by particular drugs such as anaesthetics, as well as by non-pharmacological factors such as sleep, and its dysfunction has been implicated in central nervous system disorders such as Alzheimer disease. Although the glymphatic system is best described in rodents, reports using multiple neuroimaging modalities indicate that a similar transport system exists in the human brain. Here, we overview the evidence for the glymphatic system and its role in disease and discuss opportunities to harness the glymphatic system therapeutically; for example, by improving the effectiveness of intrathecally delivered drugs.

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Metadata

Authors
Lohela, T. J., Lilius, T. O., & Nedergaard, M.
Affiliations
University of Copenhagen (DK)
Corresponding author
Nedergaard, Maiken
ORCID
Venue
Nature Reviews Drug Discovery
Publisher
Springer Science and Business Media LLC
Published
2022-08-10
Volume
21
Issue
10
Pages
763-779
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
DOI
10.1038/s41573-022-00500-9
OpenAlex
W4291019319
Cited by
254
References
43
Citations by year
2026: 70 · 2025: 79 · 2024: 56 · 2023: 44 · 2022: 5
FWCI
6.98
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Funders
  • Lundbeckfonden (R386--2021--165, R155-2016–552)
  • Novo Nordisk Fonden (NNF13OC0004258, NNF21OC0066419)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
glymphatic system, cerebrospinal fluid flow, interstitial fluid clearance, brain waste clearance, anesthetic agents, sleep, Alzheimer's disease, intrathecal drug delivery, brain drug delivery
MeSH terms
Glymphatic System, Alzheimer Disease, Brain, Humans

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