Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage

Abstract

✓ This study examines whether platelet-activating factor (PAF) is involved in the occurrence of vasospasm after subarachnoid hemorrhage (SAH). A vasospasm model was produced in rabbits, with animals in six experimental groups receiving two subarachnoid injections of autologous arterial blood with the addition of one of the following: saline (Control Group 1), 25% dimethyl sulfoxide (Control Group 2), PAF (1, 2.5, 5, or 10 µg), CV6209 (10 or 100 µg), BN52021 (10 or 100 µg), or anti-PAF immunoglobulin G (IgG, 50 or 500 µg). No significant differences were detected between Control Groups 1 and 2 with regard to neurological deterioration and basilar artery constriction after SAH was induced. Administration of PAF together with autologous blood aggravated neurological deficits in a dose-dependent manner (r = 0.724, p < 0.001) and produced basilar artery constriction at two doses each of 2.5 µg (p < 0.05), 5 µg (p < 0.01), and 10 µg (p < 0.01). Neurological deterioration was prevented in rabbits receiving an intracisternal administration of either PAF antagonist CV6209 or BN52021 or anti-PAF IgG (p < 0.01 at a total dose of 20 µg and p < 0.05 at a total dose of 200 µg CV6209, p < 0.01 at total doses of 20 and 200 µg BN52021, and p < 0.01 at total doses of 100 and 1000 µg anti-PAF IgG). A reduction in basilar artery constriction was achieved by the injection of anti-PAF IgG (p < 0.05 at total doses of 100 and 1000 µg). Histological examination at autopsy on Days 14 to 21 showed mainly ischemic changes in the brain, including selective neuronal necrosis and cerebral infarction. The control and PAF groups showed marked ischemic changes. On the other hand, no ischemic changes were noted in the anti-PAF IgG group, and only 9% of animals in the CV6209 group and 25% in the BN52021 group demonstrated selective neuronal necrosis or infarction. This study thus provides evidence to support the role of PAF in the pathogenesis of vasospasm after SAH.