Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.
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 less than 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 less than 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 less than 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.
Lindsberg
P J
PJ
Department of Neurology, Uniformed Services University of the Health Sciences, Hébert School of Medicine, Bethesda, Md 20814.
Yue
T L
TL
Frerichs
K U
KU
Hallenbeck
J M
JM
Feuerstein
G
G
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000097:blood / Q000503:physiopathology*; D004195:Disease Models, Animal; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C064509:BN 50739