Effect of PAF Antagonists on the Nitric Oxide Synthesis in Ischemic Cerebral Cortex

PAF 길항제가 허혈성 대뇌 피질내 Nitric Oxide 합성에 미치는 영향

  • No, Soon-Kee (Departments of Neurology, Bong-Seng Hospital) ;
  • Park, Kyu-Hyun (Departments of Neurology, College of Medicine, Pusan National University) ;
  • Lee, Won-Suk (Departments of Pharmacology, College of Medicine, Pusan National University)
  • 노순기 (봉생병원 신경과) ;
  • 박규현 (부산대학교 의과대학 신경과학교실) ;
  • 이원석 (부산대학교 의과대학 약리학교실)
  • Published : 1997.12.21

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.

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