More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction

  1. Baoqiang Li  Is a corresponding author
  2. Tatiana V Esipova
  3. Ikbal Sencan
  4. Kıvılcım Kılıç
  5. Buyin Fu
  6. Michele Desjardins
  7. Mohammad A Moeini
  8. Sreekanth Kura
  9. Mohammad A Yaseen
  10. Frederic Lesage
  11. Leif Østergaard
  12. Anna Devor
  13. David A Boas
  14. Sergei A Vinogradov
  15. Sava Sakadžić
  1. Massachusetts General Hospital, United States
  2. University of Pennsylvania, United States
  3. University of California, San Diego, United States
  4. École Polytechnique de Montréal, Canada
  5. Aarhus University, Denmark

Abstract

Our understanding of how capillary blood flow and oxygen distribute across cortical layers to meet the local metabolic demand is incomplete. We addressed this question by using two-photon imaging of resting-state microvascular oxygen partial pressure (PO2) and flow in the whisker barrel cortex in awake mice. Our measurements in layers I-V show that the capillary red-blood-cell flux and oxygenation heterogeneity, and the intracapillary resistance to oxygen delivery, all decrease with depth, reaching a minimum around layer IV, while the depth-dependent oxygen extraction fraction is increased in layer IV, where oxygen demand is presumably the highest. Our findings suggest that more homogeneous distribution of the physiological observables relevant to oxygen transport to tissue is an important part of the microvascular network adaptation to local brain metabolism. These results will inform the biophysical models of layer-specific cerebral oxygen delivery and consumption and improve our understanding of the diseases that affect cerebral microcirculation.

Data availability

All data generated or analyzed during this study are included in this paper and the supporting files.

Article and author information

Author details

  1. Baoqiang Li

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    For correspondence
    baoqiang.li@mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2992-3303
  2. Tatiana V Esipova

    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ikbal Sencan

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kıvılcım Kılıç

    Department of Neurosciences, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Buyin Fu

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michele Desjardins

    Department of Radiology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Mohammad A Moeini

    Institute of Biomedical Engineering, École Polytechnique de Montréal, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Sreekanth Kura

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Mohammad A Yaseen

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4154-152X
  10. Frederic Lesage

    Institute of Biomedical Engineering, École Polytechnique de Montréal, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Leif Østergaard

    Center of Functionally Integrative Neuroscience and MINDLab, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  12. Anna Devor

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5143-3960
  13. David A Boas

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Sergei A Vinogradov

    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4649-5534
  15. Sava Sakadžić

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (NS091230)

  • Sava Sakadžić

National Institutes of Health (MH111359)

  • Sava Sakadžić

National Institutes of Health (EB018464)

  • Sava Sakadžić

National Institutes of Health (NS092986)

  • Sava Sakadžić

National Institutes of Health (NS055104)

  • Sava Sakadžić

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

Reviewing Editor

  1. Serge Charpak, Institut National de la Santé et de la Recherche Médicale, Université Paris Descartes, France

Ethics

Animal experimentation: All animal surgical and experimental procedures were conducted following the Guide for the Care and Use of Laboratory Animals and approved by the Massachusetts General Hospital Subcommittee on Research Animal Care (Protocol No.: 2007N000050).

Version history

  1. Received: September 24, 2018
  2. Accepted: July 1, 2019
  3. Accepted Manuscript published: July 15, 2019 (version 1)
  4. Version of Record published: July 17, 2019 (version 2)

Copyright

© 2019, Li 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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  1. Baoqiang Li
  2. Tatiana V Esipova
  3. Ikbal Sencan
  4. Kıvılcım Kılıç
  5. Buyin Fu
  6. Michele Desjardins
  7. Mohammad A Moeini
  8. Sreekanth Kura
  9. Mohammad A Yaseen
  10. Frederic Lesage
  11. Leif Østergaard
  12. Anna Devor
  13. David A Boas
  14. Sergei A Vinogradov
  15. Sava Sakadžić
(2019)
More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction
eLife 8:e42299.
https://doi.org/10.7554/eLife.42299

Share this article

https://doi.org/10.7554/eLife.42299

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