Contribution of Platelet-Activating Factor (PAF) on Pathogenesis of Ischemic Cerebrovascular Disease

• Project/Area Number: 05671177
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Nagoya City University Medical School
• Principal Investigator: UMEMURA Atsushi (1994) Nagoya City University Medical School, Dept of Neurosurgery, Clinical Assistant, 医学部・脳神経外科, 助手 (00244567); 永井 肇 (1993) 名古屋市立大学, 医学部, 教授 (00023747)
• Co-Investigator(Kenkyū-buntansha): MABE Hideo Nagoya City University Medical School, Dept of Neu rosurgery, Assistant Professo, 医学部・脳神経外科, 助教授 (20093073) ; 梅村 淳 名古屋市立大学, 医学部, 助手 (00244567)
• Project Period (FY): 1993 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥2,000,000 (Direct Cost: ¥2,000,000); Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: focal cerebral ischemia / brain edema / platelet-activating factor

Research Abstract

Background and Purpose : Platelet-Activating Factor (PAF) is a phospholipid mediator immplicated in a diverse range of pathological processes such as allergy, inflammation, shock and trauma. Recently, a role of PAF in ischemic brain injury also has been suggested from many experimental works using PAF antagonist. In this study we examined the correlation between PAF production and progress of ischemic brain edema in focal cerebral ischemia in rats.
Methods : Focal cerebral ischemia in the are of middle cerebral artery(MCA)was induced by insertion of rubber precoated nylon thread from dissected right external carotid artery to internal carotid artery to occlude the origin of the MCA.Reperfusion was achieved by removal of the thread. The rats were divided into four experimental groups : 1) sham operated control group ; 2) 2 hours ischemia (2-0) group ; 3) 4 hours ischemia (4-0) group ; and 4) 2 hours ischemia and 2 hours reperfusion (2-2) group. As an index of brain edema, water content o f ischemic hemisphere was measured by dry-weight method. Tissue levels of PAF in ischemic hemisphere was measured by PAF [^3H] scintillation proximity assay system after extraction and isolation of PAF by Bligh-Dyer method and thin-layr chromatography.
Results : Water contents of right cerebral hemisphere in sham, 2-0,4-0 and 2-2 groups were 78.45<plus-minus>0.27,79.73<plus-minus>0.48,80.35<plus-minus>0.30 and 80.93<plus-minus>1.05%, respectively. Cerebral water content significantly increased by ischemia, and further increased by prolonged ischemia or reperfusion. On the other hand, tissue PAF levels of right cerebral hemisphere in sham, 2-0,4-0 and 2-2 groups were 4441<plus-minus>346,2298<plus-minus>409,2481<plus-minus>679 and 2901<plus-minus>930 ng/g dry weight, respectively. Tissue PAF level significantly decreased by ischemia, and slightly increased by reperfusion but still low compare
Conclusions : In this study, there was no relation between progress of ischemic brain edema and tissue PAF level in MCA occlusion in rat. Contrary to previous suggestion, tissue PAF level decreased in prolonged focal ischemia.