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Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

  1. Jordan N Norwood  Is a corresponding author
  2. Qingguang Zhang
  3. David Card
  4. Amanda Craine
  5. Timothy M Ryan
  6. Patrick J Drew  Is a corresponding author
  1. Pennsylvania State University, United States
Research Article
  • Cited 18
  • Views 3,073
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Cite this article as: eLife 2019;8:e44278 doi: 10.7554/eLife.44278

Abstract

Cerebrospinal fluid (CSF) flows through the brain, transporting chemical signals and removing waste. CSF production in the brain is balanced by a constant outflow of CSF, the anatomical basis of which is poorly understood. Here we characterized the anatomy and physiological function of the CSF outflow pathway along the olfactory sensory nerves through the cribriform plate, and into the nasal epithelia. Chemical ablation of olfactory sensory nerves greatly reduced outflow of CSF through the cribriform plate. The reduction in CSF outflow did not cause an increase in intracranial pressure (ICP), consistent with an alteration in the pattern of CSF drainage or production. Our results suggest that damage to olfactory sensory neurons (such as from air pollution) could contribute to altered CSF turnover and flow, providing a potential mechanism for neurological diseases.

Data availability

All raw data is plotted in the figures. ICP data and code (Figure 10) is included in a .zip file. Code for the analysis of actograms is available here: https://github.com/DrewLab/MedAssociates_WheelActivity

Article and author information

Author details

  1. Jordan N Norwood

    Cellular and Developmental Biology Graduate Program, Pennsylvania State University, University Park, United States
    For correspondence
    jnn120@psu.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Qingguang Zhang

    Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4500-813X
  3. David Card

    Department of Physics, Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amanda Craine

    Department of Biomedical Engineering, Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Timothy M Ryan

    Department of Anthropology, Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Patrick J Drew

    Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, United States
    For correspondence
    pjd17@psu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7483-7378

Funding

National Science Foundation (CBET1705854)

  • Patrick J Drew

National Institutes of Health (F31NS105461)

  • Jordan N Norwood

McKnight Endowment Fund for Neuroscience

  • Patrick J Drew

National Institutes of Health (R01NS078168)

  • Patrick J Drew

National Institutes of Health (P01HD078233)

  • Patrick J Drew

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The protocols used in this study were approved by the Institutional Animal Care and Use Committee (IACUC) at the Pennsylvania State University

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: December 10, 2018
  2. Accepted: May 6, 2019
  3. Accepted Manuscript published: May 7, 2019 (version 1)
  4. Version of Record published: May 17, 2019 (version 2)

Copyright

© 2019, Norwood et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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