Comparative Effects of theN-Methyl-d-aspartate Antagonist MK-801 and the Calcium Channel Blocker KB-2796 on Neurologic and Metabolic Recovery after Spinal Cord Ischemia

Abstract NMDA receptor antagonists have been demonstrated to be neuroprotective in focal cerebral ischemia and are supposed to prevent neurotoxic intracellular calcium increase. Another mechanism of calcium influx during ischemia involves activation of voltage-activated calcium channels, although the efficacy of calcium channel blockers against ischemia-induced damage varies. The purpose of this study was to determine the contributions of the excitotoxic mechanism and of calcium channel activation to metabolic and functional damage to rabbit spinal cord after ischemia induced by occlusion of the abdominal aorta. All metabolic parameters determined (ATP, energy charge, and lactate) completely recovered at 4 days following 20 min of ischemia when NMDA receptor antagonist MK-801 (1 mg/kg given iv) or calcium channel blocker KB-2796 (50 mg/kg given ip) was administered either prior to or after ischemia. Significant metabolic recovery was also observed after 30 min of ischemia with MK-801 administered before occlusion and KB-2796 given early in recirculation. Similarly, neurologic functions followed by functional performance in the hindlimbs were completely recovered following 20 and 30 min of ischemia and 4 days of recovery. This study demonstrates that although MK-801 or KB-2796 does not prevent paraplegia due to spinal cord ischemia in the rabbit, both drugs can influence the rate of recovery after ischemic injury.