IMPAIRED MITOCHONDRIAL-FUNCTION, OXIDATIVE STRESS AND ALTERED ANTIOXIDANT ENZYME-ACTIVITIES FOLLOWING TRAUMATIC SPINAL-CORD INJURY

Glutamate-induced excitotoxicity involving the formation of reactive o xygen species (ROS) has been implicated in neuronal dysfunction and ce ll loss following ischemic and traumatic injury to the central nervous system (CNS). ROS are formed in mitochondria when energy metabolism i s compromised, and are inactivated by the ROS scavengers superoxide di smutase (SOD), catalase, and glutathione (GSH). ROS can impair the fun ction of several cellular components including proteins, nucleic acids , and lipids. In the present study, we measured indicators of mitochon drial metabolic activity, ROS formation, Lipid peroxidation, and antio xidant enzyme activities in synaptosomes obtained from rat spinal cord at early times following traumatic injury. Mitochondrial metabolic ac tivity was found to significantly decrease as early as 1 h following i njury, and continued to be compromised over the remaining postinjury t ime points. ROS formation was found to be significantly increased at 4 and 24 h following injury, while lipid peroxidation levels were found to be significantly increased in the injured spinal cord at 1 and 24 h, but not 4 h following injury. SOD enzyme activity was unchanged at all postinjury time points, while catalase activity and GSH levels wer e significantly increased at 24 h following injury. These findings ind icate that impaired mitochondrial function, ROS, and lipid peroxidatio n occur soon after traumatic spinal cord injury, while the compensator y activation of molecules important for neutralizing ROS occurs at lat er time points. Therapeutic strategies aimed at facilitating the actio ns of antioxidant enzymes or inhibiting ROS formation and lipid peroxi dation in the CNS may prove beneficial in treating traumatic spinal co rd injury, provided such treatments are initiated at early stages foll owing injury. (C) 1997 Elsevier Science B.V.