University of Oulu

Bohr, T., Hjorth, P. G., Holst, S. C., Hrabětová, S., Kiviniemi, V., Lilius, T., Lundgaard, I., Mardal, K.-A., Martens, E. A., Mori, Y., Nägerl, U. V., Nicholson, C., Tannenbaum, A., Thomas, J. H., Tithof, J., Benveniste, H., Iliff, J. J., Kelley, D. H., & Nedergaard, M. (2022). The glymphatic system: Current understanding and modeling. IScience, 25(9), 104987.

The glymphatic system : current understanding and modeling

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Author: Bohr, Tomas1; Hjorth, Poul G.2; Holst, Sebastian C.3;
Organizations: 1Department of Physics, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
2Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark
3Neuroscience and Rare Diseases Discovery and Translational Area, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland
4Department of Cell Biology and The Robert Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY, USA
5Oulu Functional NeuroImaging, Department of Diagnostic Radiology, MRC, Oulu University Hospital, Oulu, Finland
6Medical Imaging, Physics and Technology, the Faculty of Medicine, University of Oulu, Oulu, Finland
7Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
8Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
9Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
10Department of Emergency Medicine and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
11Department of Experimental Medical Science, Lund University, Lund, Sweden
12Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden
13Department of Mathematics, University of Oslo, Oslo, Norway
14Simula Research Laboratory, Department of Numerical Analysis and Scientific Computing, Oslo, Norway
15Centre for Mathematical Sciences, Lund University, Sweden
16Instítut Interdisciplinaire de Neurosciences, Université de Bordeaux / CNRS UMR 5297, Centre Broca Nouvelle-Aquitaine, 146 rue Léo Saignat, CS 61292 Case 130, 33076 Bordeaux Cedex France
17Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, USA
18Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
19Departments of Computer Science/ Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA
20Department of Mechanical Engineering, University of Rochester, Rochester, 14627 NY, USA
21Department of Mechanical Engineering, University of Minnesota, Minneapolis, USA
22Department of Anesthesiology, Yale School of Medicine, New Haven, CT, USA
23Department of Biomedical Engineering, Yale School of Medicine, New Haven, CT, USA
24VISN 20 Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA
25Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA
26Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA
27Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, 14642 NY, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.4 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2023-02-16


We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid and interstitial fluid around the brain, facilitating solute transport. Models enable hypothesis development and predictions of transport, with clinical applications including drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer’s disease. We sort existing models into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, and links to neuronal activity. Needs and opportunities for future work are highlighted wherever possible; new models, expanded models, and novel experiments to inform models could all have tremendous value for advancing the field.

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Series: iScience
ISSN: 2589-0042
ISSN-E: 2589-0042
ISSN-L: 2589-0042
Volume: 25
Issue: 9
Article number: 104987
DOI: 10.1016/j.isci.2022.104987
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3112 Neurosciences
Copyright information: © 2022 The Author(s). This is an open access article under the CC BY-NC-ND license (