Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury

Shyam Gajavelli, Vishal K. Sinha, Anna T. Mazzeo, Markus S. Spurlock, Stephanie W. Lee, Aminul I. Ahmed, Shoji Yokobori, Ross M. Bullock

Research output: Contribution to journalReview article

27 Scopus citations

Abstract

Traumatic brain injury (TBI) is still the leading cause of disability in young adults worldwide. The major mechanisms – diffuse axonal injury, cerebral contusion, ischemic neurological damage, and intracranial hematomas have all been shown to be associated with mitochondrial dysfunction in some form. Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal/astrocytic metabolism to improve outcomes have been met with limited translational success. Previously, several preclinical and clinical studies on TBI induced mitochondrial dysfunction have focused on opening of the mitochondrial permeability transition pore (PTP), consequent neurodegeneration and attempts to mitigate this degeneration with cyclosporine A (CsA) or analogous drugs, and have been unsuccessful. Recent insights into normal mitochondrial dynamics and into diseases such as inherited mitochondrial neuropathies, sepsis and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. This review summarizes those aspects of mitochondrial dysfunction underlying TBI pathology with special attention to models of penetrating traumatic brain injury, an epidemic in modern American society.

Original languageEnglish (US)
Pages (from-to)133-148
Number of pages16
JournalJournal of Bioenergetics and Biomembranes
Volume47
Issue number1-2
DOIs
StatePublished - 2014

Keywords

  • Cyclosporine A
  • Hypoxia
  • KTP
  • Mitochondrial dynamics
  • Mitochondrial dysfunction
  • Penetrating traumatic brain injury
  • Secondary brain injury

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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  • Cite this

    Gajavelli, S., Sinha, V. K., Mazzeo, A. T., Spurlock, M. S., Lee, S. W., Ahmed, A. I., Yokobori, S., & Bullock, R. M. (2014). Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury. Journal of Bioenergetics and Biomembranes, 47(1-2), 133-148. https://doi.org/10.1007/s10863-014-9589-1