Formation of eicosanoids, E2/D2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain.
Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E(2) (PGE(2)) and PGD(2) could not be detected in control microwaved rat brain, suggesting little endogenous PGE(2)/D(2) production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B(2), E(2)/D(2)-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D(1), was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E(2)/D(2)-IsoPs, and docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.
Farias
Santiago E
SE
Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
Basselin
Mireille
M
Chang
Lisa
L
Heidenreich
Kim A
KA
Rapoport
Stanley I
SI
Murphy
Robert C
RC
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects*; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000378:metabolism*; D049248:Decapitation / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015777:Eicosanoids / Q000096:biosynthesis*; D028421:Isoprostanes / Q000096:biosynthesis*; D008297:Male; D008872:Microwaves; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344
D015777:Eicosanoids; D028421:Isoprostanes; D004281:Docosahexaenoic Acids; D015232:Dinoprostone; D015230:Prostaglandin D2