Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

Melanie L. McEwen, Patrick G. Sullivan, Alexander G. Rabchevsky, Joe E. Springer

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

Original languageEnglish
Pages (from-to)168-179
Number of pages12
JournalNeurotherapeutics
Volume8
Issue number2
DOIs
StatePublished - Apr 2011

Bibliographical note

Funding Information:
Preparation of the manuscript was funded by an endowment from Cardinal Hill Rehabilitation Hospital (J.E.S.) and a grant from the Craig H. Neilsen Foundation (M.L.M.). Full conflict of interest disclosure is available in the for this article.

Keywords

  • Electron transport chain
  • mitochondria
  • permeability transition
  • reactive oxygen species
  • spinal cord injury
  • therapeutic strategies

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

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