The state of brain activity modulates cerebrospinal fluid transport
Abstract
Earlier studies based on 2-photon imaging have shown that glymphatic cerebrospinal fluid (CSF) transport is regulated by the sleep-wake cycle. To examine this association, we used 3DISCO whole-body tissue clearing to map CSF tracer distribution in awake, sleeping and ketamine-xylazine anesthetized mice. The results of our analysis showed that CSF tracers entered the brain to a significantly larger extent in natural sleep or ketamine-xylazine anesthesia than in wakefulness. Furthermore, awake mice showed preferential transport of CSF tracers in the rostro-caudal direction towards the cervical and spinal cord lymphatic vessels, and hence to venous circulation and excretion by the kidneys. The study extends the current literature by showing that CSF dynamics on the whole-body scale is controlled by the state of brain activity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glymphatic fluid transport is enhanced during sleep.
“Glymphatic fluid transport is enhanced during sleep14–19.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [19]
The results provide further support to prior studies that identified sleep as a key driver of glymphatic flow in the rodent and human brain.
“The results presented here provide further support to prior studies that identified sleep as a key driver of glymphatic flow in the rodent and human brain14,16,19,63.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [19]
Cites
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., et al. (2019) · Science · doi:10.1126/science.aav2546 · Cited by 813 · see citing works
Circadian control of brain glymphatic and lymphatic fluid flow
Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., Nguyen, R., Benrais, A., & Nedergaard, M. (2020) · Nature Communications · doi:10.1038/s41467-020-18115-2 · Cited by 704 · see citing works
Self-citationRoh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J., & Holtzman, D. M. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004291 · Cited by 563 · see citing works
Cerebrospinal fluid influx drives acute ischemic tissue swelling
Mestre, H., Du, T., Sweeney, A. M., Liu, G., Samson, A. J., Peng, W., Mortensen, K. N., Stæger, F. F., Bork, P. A. R., Bashford, L., et al. (2020) · Science · doi:10.1126/science.aax7171 · Cited by 494 · see citing works
Self-citationSleep is of the brain, by the brain and for the brain
Hobson, J. A. (2005) · Nature · doi:10.1038/nature04283 · Cited by 440 · see citing works
Zou, W., Pu, T., Feng, W., Lu, M., Zheng, Y., Du, R., Xiao, M., & Hu, G. (2019) · Translational Neurodegeneration · doi:10.1186/s40035-019-0147-y · Cited by 396 · see citing works
He, X.-F., Liu, D.-X., Zhang, Q., Liang, F.-Y., Dai, G.-Y., Zeng, J.-S., Pei, Z., Xu, G.-Q., & Lan, Y. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00144 · Cited by 371 · see citing works
Brain Extracellular Space: The Final Frontier of Neuroscience
Nicholson, C., & Hrabětová, S. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.06.052 · Cited by 321 · see citing works
Bojarskaite, L., Vallet, A., Bjørnstad, D. M., Gullestad Binder, K. M., Cunen, C., Heuser, K., Kuchta, M., Mardal, K.-A., & Enger, R. (2023) · Nature Communications · doi:10.1038/s41467-023-36643-5 · Cited by 149 · see citing works
Sleep Disturbances in Frontotemporal Dementia
McCarter, S. J., St. Louis, E. K., & Boeve, B. F. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0680-3 · Cited by 80 · see citing works
Sleep in Neurodegenerative Disorders
Malkani, R., & Attarian, H. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-015-0016-x · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep
Hauglund, N. L., Andersen, M., Tokarska, K., Radovanovic, T., Kjaerby, C., Sørensen, F. L., Bojarowska, Z., Untiet, V., Ballestero, S. B., Kolmos, M. G., et al. (2025) · Cell · doi:10.1016/j.cell.2024.11.027 · Cited by 349 · see citing works
Self-citation
- Authors
- Miyakoshi, L. M., Stæger, F. F., Li, Q., Pan, C., Xie, L., Kang, H., Pavan, C., Dang, J., Sun, Q., Ertürk, A., & Nedergaard, M.
- ORCID
- Nedergaard, Maiken
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 229
- Pages
- 102512
- ISSN
- 0301-0082
- Cited by
- 26
- References
- 11
- Language
- en
- Licence
- Funders
- EU Joint Programme – Neurodegenerative Disease Research
- Human Frontier Science Program (RGP0036)
- National Institutes of Health (R01AT011439, U19NS128613)
- Lundbeck Foundation (R386-2021-165)
- Army Research Office (MURI W911NF1910280)
- Novo Nordisk Fonden (NNF20OC0066419)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Simons Foundation (811237)
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 ›
Are you an author, or do you see a problem with this page? Request a review