2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline reduces glial loss and acute white matter pathology after experimental spinal cord contusion

Focal microinjection of 2,3-dihyro-6-nitro-7-sulfamoylbenzo(f)quinoxaline ( NBQX), an antagonist of the AMPA/kainate subclass of glutamate receptors, r educes neurological deficits and tissue loss after spinal cord injury. Dose -dependent sparing of white matter is seen at 1 month after injury that is correlated to the dose-related reduction in chronic functional deficits. To determine whether NBQX exerts an acute effect on white matter pathology, f emale, adult Sprague Dawley rats were subjected to a standardized weight dr op contusion at T-8 (10 gm x 2.5 cm) and NBQX (15 nmol) or vehicle (VEH) so lution focally injected into the injury site 15 min later. At 4 and 24 hr, tissue from the injury epicenter was processed for light and electron micro scopy, and the histopathology of ventromedial white matter was compared. Th e axonal injury index, a quantitative representation of axoplasmic and myel inic pathologies, was significantly lower in the NBQX group at 4 hr (2.7 +/ - 0.24, mean +/- SE) and 24 hr (1.4 +/- 0.19) than in VEH controls (3.8 +/- 0.33 and 2.1 +/- 0.20, respectively). Counts of glial cell nuclei indicate d a loss of at least 60% at 4 and 24 hr after injury in the VEH group compa red with uninjured controls. NBQX treatment reduced this glial loss by half . Immunohistochemistry revealed that the spared glia were primarily oligode ndrocytes. Thus, the chronic effects of NBQX in reducing white matter loss after spinal cord injury appear to be attributable to the reduction of acut e pathology and may be mediated through the protection of glia, particularl y oligodendrocytes.