Neuroprotective effect of NS-7, a novel Na+ and Ca2+ channel blocker, in a focal ischemic model in the rat.
NS-7 is a novel, voltage-dependent Na(+) and Ca(2+) channel blocker. This study evaluated the in vivo neuroprotective effect of NS-7 in a rat transient focal ischemic model when administered during occlusion. Left middle cerebral artery occlusion was induced in adult male Sprague-Dawley rats for 120 min using an intraluminal thread method. The rats received a single intravenous injection of NS-7 or saline (control group) just after the onset of ischemia, and at 30, 60 and 120 min after ischemia. Their brains were removed after 48 h reperfusion, sectioned, and stained with hematoxylin and eosin. Animals were evaluated by neurological examination at 120 min ischemia and 48 h reperfusion. Infarcted cortex and striatum were measured quantitatively and infarction volumes were calculated. Cortical infarction volumes were 128+/-74 (NS-7) and 214+/-64 mm(3) (control) immediately after the ischemia group, 155+/-48 (NS-7) and 225+/-12 mm(3) (control) after the 30 min group, 160+/-54 (NS-7) and 225+/-48 mm(3) (control) after the 60 min group, and 176+/-43 (NS-7) and 223+/-38 mm(3) (control) after the 120 min group. Cortices in NS-7-treated groups were significantly less infarcted than in control groups at all treatment times. There was no significant difference in the striatal infarction volume between the treatment and control groups. Neurological examination showed that hemiparesis and abnormal posture of the NS-7 groups were significantly more improved at 48 h reperfusion than those of the control groups without posture examination in the 120 min group. These observations suggest that NS-7 may be a new potential therapeutic agent for the acute phase of cerebral infarction.
Katsumata
Toshiya
T
The Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan. katumata@nms.ac.jp
Muramatsu
Hiromi
H
Nakamura
Hidenori
H
Nishiyama
Yutaka
Y
Aoki
Yasuaki
Y
Katayama
Yasuo
Y
D000818:Animals; D001921:Brain / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013997:Time Factors
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D011743:Pyrimidines; D026941:Sodium Channel Blockers