The therapeutic efficacy of intrathecally administered
MK-801 (
dizocilpine maleate), a noncompetitive receptor antagonist of
N-methyl-D-aspartate receptor complex, was investigated in a rabbit
spinal cord ischemia model.
Normal saline, 0.3 ml (control, n = 4) or
MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta
silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with
MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by
MK-801 pretreatment and by 87, 66, and 46%, respectively, by
MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of
MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII-X. Intrathecal administration of
MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.