Role of arachidonic acid metabolism on ischemic brain edema and metabolism.
Arachidonic acid is liberated from damaged cell membranes during ischemia and is the source of vasoactive prostanoids. In this study, specific drugs that influence AA metabolism were investigated for their effects on brain edema and energy metabolites during ischemia. The agents tested were: methylprednisolone (phospholipase A2 inhibition), indomethacin (cyclooxygenase inhibitor), trapidil (TXA2 synthetase inhibitor), and OP-41483 (prostacyclin derivative). Cerebral ischemia was produced using bilateral common carotid artery occlusion in spontaneously hypertensive rats. Brain water content and concentrations of ATP, pyruvate, and lactate were determined 3 hr after occlusion. Compared with its vehicle, methylprednisolone significantly reduced water content and lactate concentration and maintained high levels of ATP. Indomethacin had no effect on brain water content nor metabolite levels. Trapidil decreased water content and lactate levels and increased levels of ATP and pyruvate. OP-41483 had no effect on water content and lactate, but maintained ATP and pyruvate at high levels. These results indicate that some of the AA metabolites may play an important role in the development of brain edema and in the impairment of energy metabolism.
Katayama
Y
Y
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Shimizu
J
J
Suzuki
S
S
Memezawa
H
H
Kashiwagi
F
F
Kamiya
T
T
Terashi
A
A
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications*; D004734:Energy Metabolism / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D006973:Hypertension / Q000150:complications; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008775:Methylprednisolone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014192:Trapidil / Q000494:pharmacology
D001095:Arachidonic Acids; D008563:Membrane Lipids; D016718:Arachidonic Acid; D011464:Epoprostenol; D014192:Trapidil; C035847:ataprost; D008775:Methylprednisolone; D007213:Indomethacin