Alterations of the eicosanoid synthetic capacity of rat brain microvessels following ischemia: relevance to ischemic brain edema.
To know the mechanism underlying ischemic brain edema, a time-course analysis of the eicosanoid synthetic capacity of brain microvessels was carried out using unilateral, middle cerebral artery (MCA)-occluded rats. Concomitant with the development of brain edema the synthetic capacity of all products, including cyclooxygenase and lipoxygenase products, increased significantly. Next the effects of 15-hydroperoxyarachidonic acid (15-HPAA) on the synthetic capacity of microvessels were examined. The drug caused a generalized increase of each product, the profile of which was similar to that obtained with ischemic hemispheres, although the ratios of each product differed somewhat among them. The enhanced synthesis of eicosanoids by 15-HPAA was markedly suppressed by radical scavengers such as alpha-tocopherol, hydroquinone, and 1,2-bis(nicotineamide)-propane. Furthermore, the evolution of brain edema was virtually suppressed by the systemic administration of 1,2-bis(nicotineamide)-propane. The above result suggests that the enzyme activity of the arachidonic acid (AA) cascade of microvessels is stimulated by its own products. Such a mechanism will form a vicious cycle that accelerates the accumulation of free radicals within microvessels and thus may play a role in the progressing disruption of the blood-brain barrier (BBB) following ischemia.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001834:Body Water / Q000032:analysis; D001923:Brain Chemistry; D001929:Brain Edema / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004537:Eicosanoic Acids / Q000378:metabolism*; D005609:Free Radicals; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D011188:Potassium / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000032:analysis; D013997:Time Factors
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D005609:Free Radicals; D015289:Leukotrienes; D008054:Lipid Peroxides; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D012964:Sodium; D011188:Potassium