The effect of a platelet activating factor antagonist (BN 52021) on neurologic outcome and histopathology in a canine model of complete cerebral ischemia.

Abstract

Research has demonstrated that platelet activating factor may modulate, in part, the severity of postischemic neurologic injury. The proposed mechanism involves a platelet activating factor-mediated release of cerebral cellular lipids and free fatty acids, resulting in increased cerebral edema and cell injury. The present study tested the hypothesis that a specific platelet activating factor antagonist, BN 52021, would improve neurologic outcome after 12 min of complete global cerebral ischemia in a canine model. Using an established canine model of complete cerebral ischemia, dogs were assigned randomly to receive, in a blinded fashion, either 20 mg/kg BN 52021 intravenously (N = 8) or placebo (N = 7) 5 min before cerebral ischemia. After cerebral ischemia and recovery, neurologic assessment was performed by a blinded observer for 72 h. Immediately thereafter, the brains were harvested and later were evaluated histologically by a neuropathologist blinded to the treatment groups. Dogs were well matched for systemic physiologic variables during all portions of the study. One placebo-treated dog and one BN 52021-treated dog were not included in the statistical analysis because of failure to meet preestablished protocol criteria. BN 52021, when compared to placebo, affected neither neurologic functional recovery nor overall histopathology scores. Regional histopathology was improved in BN 52021-treated dogs in only 1 of 18 brain regions studied (i.e., the parietal cortex). When both treatment groups were combined, there was a significant correlation between neurologic function rank and histopathology rank. The present data demonstrate that the platelet activating factor antagonist BN 52021, at a dose of 20 mg/kg intravenously given 5 min before cerebral ischemia, did not protect the brain from injury in this canine model of complete global ischemia.