Effect of phorbol myristate acetate on cerebral blood flow in normal and neutrophil-depleted rats

Abstract

Background and Purpose: Recent evidence suggests a possible role for leukocytes in ischemic brain injury. This study examined the effect of activation of endogenous circulating leukocytes on cerebral blood flow in normal and neutrophil-depleted rats. Methods: Leukocytes were activated by rapid injection of either 50 μg/kg phorbol 12-myristate 13-acetate, a protein kinase C activator, or an equimolar amount of the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine, into the right carotid artery. Control rats received an equal volume of dimethyl sulfoxide in saline vehicle. H2-clearance cerebral blood flow was measured in each of the three groups and in vinblastine-treated, neutrophil-depleted rats after carotid artery injection of phorbol. Results: Phorbol 12-myristate 13-acetate dramatically decreased circulating leukocyte and platelet counts from 5 to 120 minutes after infusion and decreased regional cerebral blood flow in the ipsilateral parietal cortex from a baseline of 119±14 mL • min-1 • 100 g-1 (mean±SEM) to 49±5 mL • min-1 • 100 g-1 at 30 minutes (P.05 versus baseline) by 90 to 120 minutes. Conclusions: The early phorbol 12-myristate 13-acetate-induced decrease in cerebral blood flow may be due to the effects of protein kinase C activation on vascular smooth muscle or on platelet aggregation, whereas the persistent decrease in cerebral blood flow appears to be mediated in part by neutrophil activation. © 1993 American Heart Association, Inc.