Jr. Wrathall et al., AMELIORATION OF FUNCTIONAL DEFICITS FROM SPINAL-CORD TRAUMA WITH SYSTEMICALLY ADMINISTERED NBQX, AN ANTAGONIST OF NON-N-METHYL-D-ASPARTATE RECEPTORS, Experimental neurology, 137(1), 1996, pp. 119-126
Excitatory amino acid (EAA) receptors play a significant role in delay
ed neuronal death after ischemic and traumatic injury to the CNS. Rece
nt data based on focal microinjection experiments have demonstrated th
at ,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), a highly
selective and potent antagonist of non-N-methyl-D-aspartate ionotropi
c EAA receptors, i.e., those preferring alpha-amino-3-hydroxy-5-methyl
-4-isoxazole propionic acid (AMPA) or kainate, can reduce histopatholo
gy and functional deficits after traumatic spinal cord injury (SCI). T
hus, non-NMDA receptors at or near the injury site appear to be import
ant in secondary injury processes that contribute significantly to the
consequences of SCI. We have now examined the effects of systemic NBQ
X, using intravenous infusion, the most commonly used and temporally e
fficient clinical mode of drug administration. Standardized contusive
SCI was produced at the T8 vertebral level in Sprague-Dawley rats. Beg
inning at 15 min postinjury, NBQX was administered intravenously at 1
mg/kg/min for 30 min. Behavioral tests of hindlimb functional deficits
were performed at 1 day and weekly for 1 month after SCI. Spinal cord
tissue was then examined morphometrically to compare lesion size and
amount of spared tissue. We found that intravenous administration of N
BQX significantly reduced functional impairment after SCI. The effects
included more rapid and extensive recovery of hindlimb reflexes, more
rapid establishment of a reflex bladder, and a more rapid and greater
degree of recovery of coordinated use of hindlimbs in open field loco
motion, swimming, and maintaining position on an inclined plane. The p
rofile of effects was similar to that seen with focal microinjection o
f NBQX, suggesting that even with systemic administration, the drug ac
ts mainly at the injury site. Further, the results support a therapeut
ic potential for NBQX, or similar drugs that antagonize non-NMDA recep
tors and inhibit secondary injury processes after SCI. (C) 1996 Academ
ic Press, Inc.