The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord

Ying Jin, Melanie L. McEwen, Stephanie A. Nottingham, William F. Maragos, Natasha B. Dragicevic, Patrick G. Sullivan, Joe E. Springer

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

The purpose of this study was to investigate the potential neuroprotective efficacy of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in rats following a mild to moderate spinal cord contusion injury. Animals received intraperitoneal injections of vehicle (DMSO) or 5 mg/mL of DNP prior to injury. Twenty-four hours following surgery, mitochondrial function was assessed in mitochondria isolated from spinal cord synaptosomes. In addition, synaptosomes were used to measure indicators of reactive oxygen species formation, lipid peroxidation, and protein oxidation. Relative to vehicle-treated animals, pretreatment with DNP maintained mitochondrial bioenergetics and significantly decreased reactive oxygen species levels, lipid peroxidation, and protein carbonyl content following spinal cord injury. Furthermore, pretreatment with DNP significantly increased the amount of remaining white matter at the injury epicenter 6 weeks after injury. These results indicate that treatment with mitochondrial uncoupling agents may provide a novel approach for the treatment of secondary injury following spinal cord contusion.

Original languageEnglish
Pages (from-to)1396-1404
Number of pages9
JournalJournal of Neurotrauma
Volume21
Issue number10
DOIs
StatePublished - Oct 2004

Keywords

  • Lipid peroxidation
  • Mitochondrial membrane potential
  • Protein carbonyl
  • Reactive oxygen species
  • Spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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