Mechanisms of cerebral protection by pentobarbital and nizofenone correlated with the course of local cerebral blood flow changes.

Abstract

The effects of delayed administration of pentobarbital and a novel imidazole derivative (Nizofenone or Y-9179) on the infarction size following the regional cerebral ischemia were studied using the permanent middle cerebral artery (MCA) occlusion model in cats. The courses of local cerebral blood flow (lCBF) before and after drug administration were also studied using the hydrogen clearance method. The extent of infarction one week after MCA occlusion was significantly smaller in the drug-treated groups than in the control group. Regarding the time-course of lCBF, there was no significant differences between the control and the Y-9179 groups. On the other hand, pentobarbital administration caused a significant lCBF increase in low-flow areas where the lCBF following MCA occlusion was below 40 ml/100g/min. In spite of this flow increase, the corresponding cortical areas underwent infarction. Histological examination of the state of vasogenic edema revealed that the perivascular exudation of plasma fluid in the infarcted area was definitely less in the Y-9179 treated group than in the other groups. Results indicate that redistribution of lCBF may not be involved in the mechanism of cerebral protection by pentobarbital or Y-9179.