Temporal characterization of mitochondrial bioenergetics after spinal cord injury

Patrick G. Sullivan, Sairam Krishnamurthy, Samir P. Patel, Jignesh D. Pandya, Alexander G. Rabchevsky

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)991-999
Number of pages9
JournalJournal of Neurotrauma
Volume24
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Free radicals
  • Lipid peroxidation
  • Mitochondrial dysfunction
  • Neuronal injury
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Clinical Neurology

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