IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31257-9.html
   My bibliography  Save this article

Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease

Author

Listed:
  • Humberto Mestre

    (University of Rochester Medical Center
    University of Rochester Medical Center
    University of Pennsylvania)

  • Natasha Verma

    (University of Rochester Medical Center)

  • Thom D. Greene

    (University of Rochester Medical Center)

  • LiJing A. Lin

    (University of Rochester Medical Center)

  • Antonio Ladron-de-Guevara

    (University of Rochester Medical Center)

  • Amanda M. Sweeney

    (University of Rochester Medical Center)

  • Guojun Liu

    (University of Rochester Medical Center)

  • V. Kaye Thomas

    (University of Rochester Medical Center)

  • Chad A. Galloway

    (University of Rochester Medical Center)

  • Karen L. Mesy Bentley

    (University of Rochester Medical Center)

  • Maiken Nedergaard

    (University of Rochester Medical Center
    University of Copenhagen)

  • Rupal I. Mehta

    (University of Rochester Medical Center
    Rush University Medical Center
    Rush University Medical Center)

Abstract

Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines flow around blood vessels. Yet, we show that pia is perforated and permissive to PVS fluid flow. Furthermore, we demonstrate that pia is comprised of vascular and cerebral layers that coalesce in variable patterns along leptomeningeal arteries, often merging around penetrating arterioles. Heterogeneous pial architectures form variable sieve-like structures that differentially influence cerebrospinal fluid (CSF) transport along PVS. The degree of pial coverage correlates with macrophage density and phagocytosis of CSF tracer. In vivo imaging confirms transpial influx of CSF tracer, suggesting a role of pia in CSF filtration, but not flow restriction. Additionally, pial layers atrophy with age. Old mice also exhibit areas of pial denudation that are not observed in young animals, but pia is unexpectedly hypertrophied in a mouse model of Alzheimer’s disease. Moreover, pial thickness correlates with improved CSF flow and reduced β-amyloid deposits in PVS of old mice. We show that PVS morphology in mice is variable and that the structure and function of pia suggests a previously unrecognized role in regulating CSF transport and amyloid clearance in aging and disease.

Suggested Citation

  • Humberto Mestre & Natasha Verma & Thom D. Greene & LiJing A. Lin & Antonio Ladron-de-Guevara & Amanda M. Sweeney & Guojun Liu & V. Kaye Thomas & Chad A. Galloway & Karen L. Mesy Bentley & Maiken Neder, 2022. "Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31257-9
    DOI: 10.1038/s41467-022-31257-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31257-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31257-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Humberto Mestre & Jeffrey Tithof & Ting Du & Wei Song & Weiguo Peng & Amanda M. Sweeney & Genaro Olveda & John H. Thomas & Maiken Nedergaard & Douglas H. Kelley, 2018. "Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shelei Pan & Peter H. Yang & Dakota DeFreitas & Sruthi Ramagiri & Peter O. Bayguinov & Carl D. Hacker & Abraham Z. Snyder & Jackson Wilborn & Hengbo Huang & Gretchen M. Koller & Dhvanii K. Raval & Gra, 2023. "Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Laura Bojarskaite & Alexandra Vallet & Daniel M. Bjørnstad & Kristin M. Gullestad Binder & Céline Cunen & Kjell Heuser & Miroslav Kuchta & Kent-Andre Mardal & Rune Enger, 2023. "Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      More about this item

      Statistics

      Access and download statistics

      Corrections

      All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31257-9. See general information about how to correct material in RePEc.

      If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

      If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

      For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

      Please note that corrections may take a couple of weeks to filter through the various RePEc services.

      IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.