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 micrograms/kg phorbol 12-myristate 13-acetate, a protein kinase C activator, or an equimolar amount of the chemotactic peptide N-formyl-methionyl-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). Decreased flow persisted for the 2-hour study. Neither N-formyl-methionyl-leucyl-phenylalanine or vehicle had an effect on cerebral blood flow. In the neutrophil-depleted rats the initial decrease in cerebral blood flow at 30 and 60 minutes after infusion of phorbol was observed, but cerebral blood flow was restored to 70% to 80% of its baseline value (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.

journal_name

Stroke

journal_title

Stroke

authors

Uhl MW,Kochanek PM,Schiding JK,Nemoto EM

doi

10.1161/01.str.24.12.1977

subject

Has Abstract

pub_date

1993-12-01 00:00:00

pages

1977-82

issue

12

eissn

0039-2499

issn

1524-4628

journal_volume

24

pub_type

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