This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lindsberg, P. J. Articles by Feuerstein, G. Search for Related Content PubMed PubMed Citation Articles by Lindsberg, P. J. Articles by Feuerstein, G.

Stroke, Vol 21, 1452-1457, Copyright © 1990 by American Heart Association

ARTICLES

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

PJ Lindsberg, TL Yue, KU Frerichs, JM Hallenbeck and G Feuerstein
Department of Neurology, Uniformed Services University of the Health Sciences, Hebert School of Medicine, Bethesda, Md 20814.

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.

This article has been cited by other articles:

				K. Umemura, I. Kato, Y. Hirashima, Y. Ishii, T. Inoue, J. Aoki, N. Kono, T. Oya, N. Hayashi, H. Hamada, et al. Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia Stroke, March 1, 2007; 38(3): 1063 - 1068. [Abstract] [Full Text] [PDF]

				N. G. Bazan Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor J. Lipid Res., December 1, 2003; 44(12): 2221 - 2233. [Abstract] [Full Text] [PDF]

				D P Taggart, S M Browne, D T Wade, and P W Halligan Neuroprotection during cardiac surgery: a randomised trial of a platelet activating factor antagonist Heart, August 1, 2003; 89(8): 897 - 900. [Abstract] [Full Text] [PDF]

				S. M. Langley, P. J. Chai, J. J. Jaggers, and R. M. Ungerleider Platelet-activating factor receptor antagonism improves cerebral recovery after circulatory arrest Ann. Thorac. Surg., November 1, 1999; 68(5): 1578 - 1584. [Abstract] [Full Text] [PDF]

				M. Hiramoto, H. Yoshida, T. Imaizumi, N. Yoshimizu, and K. Satoh A Mutation in Plasma Platelet-Activating Factor Acetylhydrolase (Val279->Phe) is a Genetic Risk Factor for Stroke Stroke, December 1, 1997; 28(12): 2417 - 2420. [Abstract] [Full Text]

				J. B. Gupta, M. Prasad, J. Kalra, and K. Prasad Platelet-Activating-Factor-Induced Changes in Cardiovascular Function and Oxyradical Status of Myocardium in Presence of the PAF Antagonist CV-6209 Angiology, January 1, 1994; 45(1): 25 - 36. [Abstract] [PDF]