Induction of brain edema following intracerebral injection of arachidonic acid.
The effects of polyunsaturated fatty acids on brain edema formation have been studied in rats. Intracerebral injection of polyunsaturated fatty acids (PUFAs), including linolenic acid (18:3) and arachidonic acid (20:4), caused significant increases in cerebral water and sodium content concomitant with decreases in potassium content and Na+- and K+- dependent adenosine triphosphatase activity. There was gross and microscopic evidence of edema. Saturated fatty acids and monounsaturated fatty acid were not effective in inducing brain edema. The [125I]-bovine serum albumin spaces increased twofold and threefold at 24 hours with 18:3 and 20:4, respectively, indicating vasogenic edema with increased permeability of brain endothelial cells. Staining of the brain was observed five minutes after injection of Evans blue dye followed by arachidonic acid perfusion. A major decrease in brain potassium content was evidence of concurrent cellular (cytotoxic) edema as well. The induction of brain edema by arachidonic acid was dose dependent and maximal between 24 and 48 hours after perfusion. Dexamethasone (10 mg/kg) was effective in ameliorating the brain edema, whereas a cyclooxygenase inhibitor, indomethacin (10 mg/kg), was not. These data indicate that arachidonic acid and other PUFAs have the ability to induce vasogenic and cellular brain edema and further support the hypothesis that the degradation of phospholipids and accumulation of PUFAs, particularly arachidonic acid, initiate the development of brain edema in various disease states.
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000139:chemically induced* / Q000188:drug therapy; D002540:Cerebral Cortex; D007008:Hypokalemia / Q000139:chemically induced; D007267:Injections; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014882:Water-Electrolyte Balance / Q000187:drug effects
D001095:Arachidonic Acids; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase