Metabolic changes of arachidonic acid after cerebral ischemia-reperfusion in diabetic rats

The purpose of this study is to discuss an important component-arachidonic acid (AA) cascade of inflammatory reaction in diabetic rats with cerebral ischemia. Using the model of middle cerebral artery occlusion (MCAO), we have compared the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and measured the levels of their products prostaglandin E2 (PGE(2)) and cysteine-containing leukotrienes (cys-LTs) after different reperfusion periods in diabetic and normal rats. Cerebral ischemia-reperfusion was accompanied by increased expression of COX-2 and release of PGE2, peaking at 12 h after reperfusion. The expression of COX-2 was maintained at a high level until 24 h after reperfusion, while the levels of PGE2 were declined rapidly to baseline. The expression of 5-LOX and levels of cys-LTs reached a peak at 6 and 12 h after reperfusion, respectively, and was returned to baseline at 24 h after reperfusion. Compared with normal rats, the expression of COX-2 and 5-LOX as well as release of PGE2 and cys-LTs was elevated in the brains of diabetic rats, revealing a possible mechanism for hyperglycemia-mediated aggravation of cerebral ischemic injury. A reduction of arachidonic acid metabolites mediated by inhibitors of its metabolites could be helpful in preventing ischemic brain injury in diabetic rats. (C) 2003 Elsevier Inc. All rights reserved.