Temporal characterization of mitochondrial bioenergetics after spinal cord injury

J Neurotrauma. 2007 Jun;24(6):991-9. doi: 10.1089/neu.2006.0242.


Mitochondrial dysfunction following spinal cord injury (SCI) may be critical for the development of secondary pathophysiology and neuronal cell death. Previous studies have demonstrated a loss of mitochondrial bioenergetics at 24 h following SCI. To begin to understand the evolution and study the contribution of mitochondrial dysfunction in pathophysiology of SCI, we investigated mitochondrial bioenergetics in the mid-thoracic region at 6, 12, and 24 h following contusion SCI. It is widely accepted that increased free radical generation plays a critical role in neuronal damage after SCI. Hence, to ascertain the role of free radicals in SCI-induced mitochondrial dysfunction, markers for oxidative damage, including nitrotyrosine (3-NT), lipid peroxidation byproduct (4-hydroxynonenal [HNE]), and protein oxidation (protein carbonyls) were quantified in the same samples of isolated mitochondria during the 24-h time course. The results demonstrate that a significant decline in mitochondrial function begins to occur 12 h post-injury and persists for a least 24 h following SCI. Furthermore, there was a progressive increase in mitochondrial oxidative damage that preceded the loss of mitochondrial bioenergetics, suggesting that free radical damage may be a major mitochondrial secondary injury process. Based on the present results, the temporal profile of mitochondrial dysfunction indicates that interventions targeting mitochondrial oxidative damage and dysfunction may serve as a beneficial pharmacological treatment for acute SCI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / analysis
  • Aldehydes / metabolism
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Energy Metabolism / physiology*
  • Female
  • Free Radicals / analysis
  • Free Radicals / metabolism
  • Lipid Peroxidation / physiology
  • Mitochondria / metabolism*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / metabolism
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology*
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / physiopathology*
  • Time Factors
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Tyrosine / metabolism


  • Aldehydes
  • Free Radicals
  • Reactive Oxygen Species
  • 3-nitrotyrosine
  • Tyrosine
  • 4-hydroxy-2-nonenal