Mitochondrial damage and dysfunction in traumatic brain injury

Jonathan Lifshitz, Patrick G. Sullivan, David A. Hovda, Tadeusz Wieloch, Tracy K. McIntosh

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


The enduring cognitive deficits and histopathology associated with traumatic brain injury (TBI) may arise from damage to mitochondrial populations, which initiates the metabolic dysfunction observed in clinical and experimental TBI. The anecdotal evidence for in vivo structural damage to mitochondria corroborates metabolic and physiologic dysfunction, which depletes substrates and promotes free radical generation. Excessive calcium pathology differentially disrupts the heterogeneous mitochondrial population, such that calcium sensitivity increases after TBI. The ongoing pathology may escalate to include protein and DNA oxidation that impacts mitochondrial function and promotes cell death. Thus, in vivo TBI damages, if not eliminates, mitochondrial populations depending on injury severity, with the remaining population left to provide metabolic support for survival or repair in the wake of cellular pathology. With a considerable understanding of post-injury mitochondrial populations, therapeutic interventions targeted to the mitochondria may delay or prevent secondary cascades that lead to long-term cell death and neurobehavioral disability.

Original languageEnglish
Pages (from-to)705-713
Number of pages9
Issue number5-6 SPEC. ISS.
StatePublished - Sep 2004

Bibliographical note

Funding Information:
Supported, in part, by NIH grants NINDS P50‐30308, NINDS R01‐NS27544, NINDS R01‐NS48191, NINDS R01-NS40978, NINDS P50-NS08803, NIGMS R01-GM34690, a Veterans Administration Merit Review Grant.


  • Brain injury
  • Metabolism
  • Mitochondria

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology


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