The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema.

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.