NS-7, a novel Na+/Ca2+ channel blocker, prevents neurologic injury after spinal cord ischemia in rabbits

Objective: We investigated the neuroprotective effect of NS-7 (4-[4-fluorophenyl]-2-methyl-6-[5-piperidinopntyloxy] pyrimidine hydrochloride), a novel Na(+)/Ca(2+) channel blocker, on transient spinal cord ischemia in rabbits. Methods: Spinal cord ischemia was induced in New Zealand white rabbits by means of infrarenal aortic occlusion for 20 minutes. Four experimental groups were enrolled. A sham group (n = 3) underwent the same operation without aortic occlusion. A control group (n = 7) received only saline before occlusion. Group A (n = 8) received NS-7 (1 mg/kg) 15 minutes before ischemia, and group B (n = 8) received NS-7 (1 mg/kg) at the onset of reperfusion. Neurologic function was assessed 24 and 48 hours after the operation with modified Tarlov criteria. Spinal cords were harvested for histopathologic examination and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). Spinal cord infarction was investigated with 2, 3, 5-triphenyltetrazonlium chloride staining. Results: Tarlov scoring demonstrated marked improvement in both group A and group B compared with the control group at 24 and 48 hours after the operation. Minimal histologic changes were found in lumbar spinal cords of the 2 NS-7-treated groups, whereas severe neuronal necrosis was shown in the control group. TUNEL-positive neurons and the infarct size of lumbar spinal cords were significantly reduced by NS-7 administered both before ischemia and at the onset of reperfusion. No significant difference was noted between group A and group B in terms of spinal cord protection. Conclusion: These results indicate that NS-7 protects the spinal cord against ischemic injury by preventing both neuronal necrosis and apoptosis.