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Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep
Hauglund NL, Andersen M, Tokarska K, Radovanovic T, Kjaerby C, Sørensen FL, Bojarowska Z, Untiet V, Ballestero SB, Kolmos MG, Weikop P, Hirase H, et al.. Cell, 2025-01-08
Topic: Brain proteins, microglia and lab models
As the brain transitions from wakefulness to sleep, processing of external information diminishes while restorative processes, such as glymphatic removal of waste products, are activated. Yet, it is not known what drives brain clearance during sleep. We here employed an array of technologies and identified tightly synchronized oscillations in norepinephrine, cerebral blood volume, and cerebrospinal fluid (CSF) as the strongest predictors of glymphatic clearance during NREM sleep. Optogenetic stimulation of the locus coeruleus induced anti-correlated changes in vasomotion and CSF signal. Furthermore, stimulation of arterial oscillations enhanced CSF inflow, demonstrating that vasomotion acts as a pump driving CSF into the brain. On the contrary, the sleep aid zolpidem suppressed norepinephrine oscillations and glymphatic flow, highlighting the critical role of norepinephrine-driven vascular dynamics in brain clearance. Thus, the micro-architectural organization of NREM sleep, driven by norepinephrine fluctuations and vascular dynamics, is a key determinant for glymphatic clearance.
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APA 7th
Hauglund, N. L., Andersen, M., Tokarska, K., Radovanovic, T., Kjaerby, C., Sørensen, F. L., et al. (2025). Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. Cell. https://doi.org/10.1016/j.cell.2024.11.027
Vancouver
Hauglund NL, Andersen M, Tokarska K, Radovanovic T, Kjaerby C, Sørensen FL, et al. Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep. Cell. 2025. doi:10.1016/j.cell.2024.11.027. PMID: 39788123.
BibTeX
@article{hauglund2025-39788123,
author = {Hauglund, N. L. and Andersen, M. and Tokarska, K. and Radovanovic, T. and Kjaerby, C. and Sørensen, F. L. and Bojarowska, Z. and Untiet, V. and Ballestero, S. B. and Kolmos, M. G. and Weikop, P. and Hirase, H. and others},
title = {{Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep}},
journal = {Cell},
year = {2025},
doi = {10.1016/j.cell.2024.11.027},
pmid = {39788123},
url = {https://doi.org/10.1016/j.cell.2024.11.027}
}
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Key findings
- We here employed an array of technologies and identified tightly synchronized oscillations in norepinephrine, cerebral blood volume, and cerebrospinal fluid (CSF) as the strongest predictors of glymphatic clearance during NREM sleep.
- Optogenetic stimulation of the locus coeruleus induced anti-correlated changes in vasomotion and CSF signal.
- Furthermore, stimulation of arterial oscillations enhanced CSF inflow, demonstrating that vasomotion acts as a pump driving CSF into the brain.
- On the contrary, the sleep aid zolpidem suppressed norepinephrine oscillations and glymphatic flow, highlighting the critical role of norepinephrine-driven vascular dynamics in brain clearance.
- Thus, the micro-architectural organization of NREM sleep, driven by norepinephrine fluctuations and vascular dynamics, is a key determinant for glymphatic clearance.
Why it matters
This study identified tightly synchronized oscillations in norepinephrine, cerebral blood volume and cerebrospinal fluid as the strongest predictors of glymphatic clearance during NREM sleep, and found that the sleep aid zolpidem suppressed norepinephrine oscillations and glymphatic flow. It describes how sleep architecture drives brain waste clearance, which is relevant to understanding clearance mechanisms but does not test an Alzheimer's treatment, cure or prevention.
Study details
- Evidence strengthEarly
Limitations
The authors note that prior rodent glymphatic studies relied on anaesthesia as a surrogate for sleep, which suppresses the features of natural sleep, and that human neuroimaging lacks the resolution to quantify CSF flow in the periarterial space, so how these findings translate to humans remains open.
How this study scored 60/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 59 of the 98 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 2 / 5 | Rated “early” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 312 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 104.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 109.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 4 / 4 | Cited 312 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Maiken Nedergaard: h-index 156 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39788123) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 59 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 59 of the 98 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
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