Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: Leukotriene c4 as a possible causeof cerebral edema

Abstract

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane Bi and 6-keto prostaglandin FIq levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfbsion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C, levels. That the increased brain water content was causally related to an increase in leukotriene C, was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C, and brain water contents after reperfusion. Our results indicate that leukotriene C, is closely associated with an induction of ischemic cerebral edema. © 1988 American Heart Association, Inc.