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A clinical primer for the glymphatic system

Carlstrom, Lucas P. ; Eltanahy, Ahmed ; Perry, Avital ; Rabinstein, Alejandro A. ; Elder, Benjamin D. ; Morris, Jonathan M. ; Meyer, Fredric B. ; Graffeo, Christopher S. ; Lundgaard, Iben LU and Burns, Terry C. (2022) In Brain 145(3). p.843-857
Abstract

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic... (More)

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aging, Alzheimer's disease, beta-amyloid, glymphatic system, idiopathic normal pressure hydrocephalus
in
Brain
volume
145
issue
3
pages
15 pages
publisher
Oxford University Press
external identifiers
  • pmid:34888633
  • scopus:85129779628
ISSN
0006-8950
DOI
10.1093/brain/awab428
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021 The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
id
6ba2c908-c10b-44b2-b7a9-2552fac1ea46
date added to LUP
2022-08-19 14:58:31
date last changed
2024-06-14 12:59:33
@article{6ba2c908-c10b-44b2-b7a9-2552fac1ea46,
  abstract     = {{<p>The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science. </p>}},
  author       = {{Carlstrom, Lucas P. and Eltanahy, Ahmed and Perry, Avital and Rabinstein, Alejandro A. and Elder, Benjamin D. and Morris, Jonathan M. and Meyer, Fredric B. and Graffeo, Christopher S. and Lundgaard, Iben and Burns, Terry C.}},
  issn         = {{0006-8950}},
  keywords     = {{aging; Alzheimer's disease; beta-amyloid; glymphatic system; idiopathic normal pressure hydrocephalus}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{843--857}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{A clinical primer for the glymphatic system}},
  url          = {{http://dx.doi.org/10.1093/brain/awab428}},
  doi          = {{10.1093/brain/awab428}},
  volume       = {{145}},
  year         = {{2022}},
}