Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury

  1. David Tweedie  Is a corresponding author
  2. Hanuma Kumar Karnati
  3. Roger Mullins
  4. Chaim G Pick
  5. Barry J Hoffer
  6. Edward J Goetzl
  7. Dimitrios Kapogiannis
  8. Nigel H Greig
  1. National Institute on Aging, NIH, United States
  2. Sackler School of Medicine, Tel-Aviv University, Israel
  3. Case Western Reserve University, United States
  4. University of California Medical Center, United States

Abstract

Traumatic brain injury (TBI) is a serious global health concern, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mild model of TBI with parallels to concussive head injury. Mice (CD-1, 30–40 g) received a sham procedure or 30 g weight-drop, and were euthanized 8, 24, 48, 72, 96 hours, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins, many of which differed from sham by 8 hours post-mTBI, particularly GAS-1 and VEGF-B were increased while CXCL16 reduced, 23 proteins changed in 4 or more of the time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Validation of proteins identified in this study may provide utility as treatment response biomarkers.

Data availability

All data generated by US NIH funded research is available to the public, the data generated in this study is available to the public. The data used to generate the Figures in the manuscript are provided as source data files.

Article and author information

Author details

  1. David Tweedie

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    For correspondence
    tweedieda@grc.nia.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8446-4544
  2. Hanuma Kumar Karnati

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Roger Mullins

    Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Chaim G Pick

    Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Barry J Hoffer

    Department of Neurological Surgery, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Edward J Goetzl

    Department of Medicine, University of California Medical Center, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Dimitrios Kapogiannis

    Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nigel H Greig

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3032-1468

Funding

National Institutes of Health (AG000944)

  • Nigel H Greig

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

Ethics

Animal experimentation: AlI animal studies were conducted at the Intramural Research Program of the National Institute on Aging, Baltimore, MD, USA. Experimental animal protocols were approved by the Animal Care and Use Committee of the Intramural Research Program, National Institute on Aging (438-TGB-2022) and were in compliance with the guidelines for animal experimentation of the National Research Council (Committee for the Update of the Guide for the Care and Use of Laboratory Animals, 2011) and the National Institutes of Health (DHEW publication 85-23, revised, 1995).

Reviewing Editor

  1. Brandon K Harvey, NIDA/NIH, United States

Version history

  1. Received: February 6, 2020
  2. Accepted: August 14, 2020
  3. Accepted Manuscript published: August 17, 2020 (version 1)
  4. Accepted Manuscript updated: August 21, 2020 (version 2)
  5. Version of Record published: September 4, 2020 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. David Tweedie
  2. Hanuma Kumar Karnati
  3. Roger Mullins
  4. Chaim G Pick
  5. Barry J Hoffer
  6. Edward J Goetzl
  7. Dimitrios Kapogiannis
  8. Nigel H Greig
(2020)
Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury
eLife 9:e55827.
https://doi.org/10.7554/eLife.55827

Share this article

https://doi.org/10.7554/eLife.55827

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