Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our Genome-wide Association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction.

Article and author information

Author details

  1. Rebeccah J Katzenberger

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Stanislava Chtarbanova

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stacey A Rimkus

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie A Fischer

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gulpreet Kaur

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jocelyn M Seppala

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Laura C Swanson

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jocelyn E Zajac

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Barry Ganetzky

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. David A Wassarman

    Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
    For correspondence
    dawassarman@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Utpal Banerjee, University of California, Los Angeles, United States

Publication history

  1. Received: September 17, 2014
  2. Accepted: March 5, 2015
  3. Accepted Manuscript published: March 5, 2015 (version 1)
  4. Version of Record published: March 30, 2015 (version 2)

Copyright

© 2015, Katzenberger 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. Rebeccah J Katzenberger
  2. Stanislava Chtarbanova
  3. Stacey A Rimkus
  4. Julie A Fischer
  5. Gulpreet Kaur
  6. Jocelyn M Seppala
  7. Laura C Swanson
  8. Jocelyn E Zajac
  9. Barry Ganetzky
  10. David A Wassarman
(2015)
Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction
eLife 4:e04790.
https://doi.org/10.7554/eLife.04790

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