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.


CONCLUSIONS
These results indicate that NS-7 protects the spinal cord against ischemic injury by preventing both neuronal necrosis and apoptosis.
Shi
Enyi
E
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Kazui
Teruhisa
T
Jiang
Xiaojing
X
Washiyama
Naoki
N
Suzuki
Kazuchika
K
Yamashita
Katsushi
K
Terada
Hitoshi
H
D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D035002:Lower Extremity / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D011743:Pyrimidines / Q000037:antagonists & inhibitors*; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020196:Trauma, Nervous System / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D011743:Pyrimidines; D026941:Sodium Channel Blockers