Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion

W. Brad Hubbard, Hemendra J. Vekaria, Olivia J. Kalimon, Malinda L. Spry, Emily P. Brown, Todd J. Kilbaugh, Patrick G. Sullivan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Pioglitazone interacts through the mitochondrial protein mitoNEET to improve brain bioenergetics following traumatic brain injury. To provide broader evidence regarding the therapeutic effects of pioglitazone after traumatic brain injury, the current study is focused on immediate and delayed therapy in a model of mild brain contusion. To assess pioglitazone therapy on mitochondrial bioenergetics in cortex and hippocampus, we use a technique to isolate subpopulations of total, glia-enriched and synaptic mitochondria. Pioglitazone treatment was initially administered at either 0.25, 3, 12 or 24h following mild controlled cortical impact. At 48h post-injury, ipsilateral cortex and hippocampus were dissected and mitochondrial fractions were isolated. Maximal mitochondrial respiration injury-induced deficits were observed in total and synaptic fractions, and 0.25h pioglitazone treatment following mild controlled cortical impact was able to restore respiration to sham levels. While there are no injury-induced deficits in hippocampal fractions, we do find that 3h pioglitazone treatment after mild controlled cortical impact can significantly increase maximal mitochondrial bioenergetics compared to vehicle-Treated mild controlled cortical impact group. However, delayed pioglitazone treatment initiated at either 3 or 24h after mild brain contusion does not improve spared cortical tissue. We demonstrate that synaptic mitochondrial deficits following mild focal brain contusion can be restored with early initiation of pioglitazone treatment. Further investigation is needed to determine functional improvements with pioglitazone beyond that of overt cortical tissue sparing following mild contusion traumatic brain injury.

Original languageEnglish
Article numberfcad032
JournalBrain Communications
Issue number2
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.


  • TBI
  • bioenergetics
  • mitoNEET
  • oxidative stress
  • traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience


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