Korean J Physiol Pharmacol.  1997 Dec;1(6):665-672.

Effect of PAF antagonists on the nitric oxide synthesis in ischemic cerebral cortex

Affiliations
  • 1Department of Pharmacology, College of Medicine, Pusan National University Pusan 602-739, South Korea.
  • 2Department of Neurology, College of Medicine, Pusan National University, Pusan 602-739, South Korea.
  • 3Department of Neurology, Bong-Seng Hospital, Pusan 601-051, South Korea.

Abstract

This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor (PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery (MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.

Keyword

Cerebral ischemia; PAF antagonists; Nitric oxide
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