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 i.v.) or
calcium channel blocker KB-2796 (50 mg/kg given i.p.) 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.