Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits

Abstract

Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed platelets to be elevated by approximately 20-fold in spinal cord injured by 25 minutes of ischemia and 2 hours of reperfusion (2.80±0.98 ng/g) compared with that in normal spinal cord (0.15±0.06 ng/g, p<0.01). Given during ischemia to seven rabbits, 10 mg/kg i.p. of a highly selective and potent antagonist of platelet-activating factor (BN 50739) accentuated the early postischemic hyperemia and prevented the delayed hypoperfusion measured by on-line laser-Doppler flowmetry (-35±7% of baseline [n=7] without versus 33±14% with treatment, p< 0.01) and the edema formation measured as the increase in tissue water content (4.4±0.7% without [n=6] versus 2.1 ±0.6% with [n=7] treatment, p< 0.05) after 2 hours of reperfusion. This neurochemical and pharmacologic evidence emphasizes a new perspective of ischemia-induced phospholipid degradation and suggests an important role for platelet-activating factor in the early manifestations of stroke. © 1990 American Heart Association, Inc.