title: NBQX treatment improves mitochondrial function and reduces oxidative events after spinal cord injury.
abstract: The purpose of this study was to examine the effects of inhibiting ionotropic glutamate receptor subtypes on measures of oxidative stress events at acute times following traumatic spinal cord injury (SCI). Rats received a moderate contusion injury and 15 min later were treated with one of two doses of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulfonamide disodium (NBQX), MK-801, or the appropriate vehicle. At 4 h following injury, spinal cords were removed and a crude synaptosomal preparation obtained to examine mitochondrial function using the MTT assay, as well as measures of reactive oxygen species (ROS), lipid peroxidation, and glutamate and glucose uptake. We report here that intraspinal treatment with either 15 or 30 nmol of NBQX improves mitochondrial function and reduces the levels of ROS and lipid peroxidation products. In contrast, MK-801, given intravenously at doses of 1.0 or 5.0 mg/kg, was without effect on these same measures. Neither drug treatment had an effect on glutamate or glucose uptake, both of which are reduced at acute times following SCI. Previous studies have documented that drugs acting on non-N-methyl-D-aspartate (NMDA) receptors exhibit greater efficacy compared to NMDA receptor antagonists on recovery of function and tissue sparing following traumatic spinal cord injury. The results of this study provide a potential mechanism by which blockade of the non-NMDA ionotropic receptors exhibit positive effects following traumatic SCI.
authors.affiliation: Department of Anatomy, Center for Spinal Cord and Brain Injury Research, University of Kentucky Medical Center, Lexington, Kentucky 40536-0084, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Mu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Azbill
authors.forename: Joe E
authors.initials: JE
authors.lastname: Springer
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007278:Injections, Spinal; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D013574:Synaptosomes / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013904:Thoracic Vertebrae
chemical_list: D016291:Dizocilpine Maleate; D005947:Glucose; D018698:Glutamic Acid; D018696:Neuroprotective Agents; D011810:Quinoxalines; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017392:Thiobarbituric Acid Reactive Substances; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline