The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord.
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.
Jin
Ying
Y
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Cardinal Hill Rehabilitation Hospital, Lexington, Kentucky 40536, USA.
McEwen
Melanie L
ML
Nottingham
Stephanie A
SA
Maragos
William F
WF
Dragicevic
Natasha B
NB
Sullivan
Patrick G
PG
Springer
Joe E
JE
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology / Q000517:prevention & control*; D014475:Uncoupling Agents / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D019297:2,4-Dinitrophenol