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. 2025 Apr;28(4):731-733.
doi: 10.1038/s41593-025-01897-3. Epub 2025 Mar 11.

A curious concept of CNS clearance

Virginia Plá #  1 , Erik Kroesbergen #  1 , Saiyue Deng  1 , Michael J Giannetto  2 , Lauren M Hablitz  2 , Evan Newbold  2 , Antonio Ladrón-de-Guevara  2 , Tina Esmail  1 , Ryszard Stefan Gomolka  1 , Yuki Mori  1 , Steven A Goldman  1   2 , Douglas H Kelley  3 , John H Thomas  3 , Maiken Nedergaard  4   5
Affiliations

A curious concept of CNS clearance

Virginia Plá et al. Nat Neurosci. 2025 Apr.
No abstract available

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Conflict of interest statement

Competing interests: The authors declare no competing interests. M.N. is a paid consultant for CNS2 for unrelated work.

Figures

Fig. 1.
Fig. 1.. Discrepancy between flow velocity model and actual velocity.
Equation 6 models velocity as purely radial, emanating from the origin, whose location is not stated but presumably is the centre of the observation region (right). However, the experiment being modeled involved no such outward flow; rather, the velocity pointed downward (left). Depending on the location, downward flow is either aligned with, orthogonal to, or in direct opposition to outward flow. Additionally, the modeled flow fails to conserve fluid mass, making it impossible. Equation 6 cannot be used to model the experiment shown in Extended Data Figure 5 of Miao et al. or any others.
Fig. 2:
Fig. 2:. Data visualization, unequal sampling, and improper statistical analysis may cause interpretation errors in diurnal variation of diffusion.
(A) The original manuscript Figure 1e (green shaded boxes, data ranges). (B) Data re-graphed to show data variability and four-hour intervals (red dots, individual animals; error bars mean ± SEM; gray box, dark phase). (C) Tukey boxplot showing statistical outliers in the ZT0–4 and ZT20–24 bins (red dots). (D) Data re-plotted without outliers in C, with the significant ZT8–12 and ZT2–24 comparison (inset) (red dots, individual animals; error bars mean ± SEM; gray box, dark phase; *p = 0.0413).
See this image and copyright information in PMC

References

    1. Kang JE, et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326, 1005–1007 (2009). - PMC - PubMed
    1. Holth JK, et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science 363, 880–884 (2019). - PMC - PubMed
    1. Shokri-Kojori E, et al. beta-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A 115, 4483–4488 (2018). - PMC - PubMed
    1. Xie L, et al. Sleep drives metabolite clearance from the adult brain. Science 342, 373–377 (2013). - PMC - PubMed
    1. Eide PK, Vinje V, Pripp AH, Mardal KA & Ringstad G Sleep deprivation impairs molecular clearance from the human brain. Brain 144, 863–874 (2021). - PubMed