title: Temporal characterization of mitochondrial bioenergetics after spinal cord injury.
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.
authors.affiliation: Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky 40536-0509, USA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Sullivan
authors.forename: Sairam
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Samir P
authors.initials: SP
authors.lastname: Patel
authors.forename: Jignesh D
authors.initials: JD
authors.lastname: Pandya
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Rabchevsky
mesh_terms: D000447:Aldehydes / Q000032:analysis / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005609:Free Radicals / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
chemical_list: D000447:Aldehydes; D005609:Free Radicals; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal