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doi:10.1016/j.lfs.2005.04.083 
Copyright © 2005 Elsevier Inc. All rights reserved.
Chronic administration of ethyl docosahexaenoate decreases mortality and cerebral edema in ischemic gerbils
Received 20 April 2004;
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Abstract
Dietary docosahexaenoic acid (DHA) intake can decrease the level of membrane arachidonic acid (AA), which is liberated during cerebral ischemia and implicated in the pathogenesis of brain damage. Therefore, in the present study, we investigated the effects of chronic ethyl docosahexaenoate (E-DHA) administration on mortality and cerebral edema induced by transient forebrain ischemia in gerbils. Male Mongolian gerbils were orally pretreated with either E-DHA (100, 150 mg/kg) or vehicle, once a day, for 4 weeks and were subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. The content of brain lipid AA at the termination of treatment, the survival ratio, change of regional cerebral blood flow (rCBF), brain free AA level, thromboxane B2 (TXB2) production and cerebral edema formation following ischemia and reperfusion were evaluated. E-DHA (150 mg/kg) pretreatment significantly increased survival ratio, prevented post-ischemic hypoperfusion and attenuated cerebral edema after reperfusion compared with vehicle, which was well associated with the reduced levels of AA and TXB2 in the E-DHA treated brain. These data suggest that the effects of E-DHA pretreatment on ischemic mortality and cerebral edema could be due to reduction of free AA liberation and accumulation, and its metabolite synthesis after ischemia and reperfusion by decreasing the content of membrane AA.
Keywords: Ethyl docosahexaenoate; Arachidonic acid; Transient forebrain ischemia; Survival ratio; Cerebral edema; Regional cerebral blood flow; Gerbil
Abbreviations: AA, arachidonic acid; DHA, docosahexaenoic acid; E-DHA, ethyl docosahexaenoate; EPA, eicosapentaenoic acid; FAMEs, fatty acid methyl esters; LT, leukotriene; MABP, mean arterial blood pressure; NO, nitric oxide; rCBF, regional cerebral blood flow; PG, prostaglandin; PGG2, prostaglandin G2; PGH2, prostaglandin H2; PGI2, prostaglandin I2; PGI3, prostaglandin I3; PLA2, phospholipase A2; TLC, thin-layer chromatograph; TX, thromboxane; TXA2, thromboxane A2; TXA3, thromboxane A3; TXB2, thromboxane B2
