Title: Protective effect of nizofenone against cerebral ischemia in mice.
Abstract: The susceptibility of various experimental animals to global ischemia following bilateral occlusion of common carotid arteries was investigated. When animals were subjected to bilateral ligation of the common carotid arteries, the susceptibility varied greatly depending on the species or strains. Rats (Sprague-Dawley and Wistar strains) were highly resistant to global ischemia following bilateral carotid occlusion. Gerbils were susceptible to global ischemia, as expected: 70 % died within 2 hr after ligation and 95 % within 6 hr. The ICR strain of mouse was found to be more susceptible to global ischemia than gerbils: about 10 min after bilateral carotid occlusion, tremors, myoclonus and then intermittent attacks were observed, with 80 % of the animals dying within 1 hr, and most of the others failing to survive more than 4 hr. Pretreatment with nizofenone dose-dependently increased survival time remarkably, with 15-25 % of each of the high dose groups (3 mg /kg i.p. or more) surviving over 20 hr. The protective action of nizofenone was also confirmed in experiments with the dd strain of mouse, which was also vulnerable to global ischemia, although not as spectacularly as the ICR strain. The present study indicates that mice are greatly susceptible to global ischemia, and nizofenone is useful in treatment of ischemic brain injury.