Induction of brain edema following intracerebral injection of arachidonic acid

Abstract

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.

Dexamethasone and Indomethacin Do Not Affect Brain Edema following Head Injury in Rats

“…These latter findings agree with those reported by Chan et al (1983) who demon strated that neither indomethacin nor dexametha sone per se had an effect on brain water content of control animals. These investigators induced vaso genic brain edema in rats by intracerebral injection of arachidonic acid.…”

Influence of Granulocytes on Brain Edema, Intracranial Pressure, and Cerebrospinal Fluid Concentrations of Lactate and Protein in Experimental Meningitis

“…Extensive work by Fishman et al [23], Chan and Fishman [24], and Chan et al [25] has implicated granulocytes as an important factor in development of brain edema. Both arachidonic acid and other free polyunsaturated fatty acids [38][39][40], which represent major constituents of the granulocytic cell wall and are found in high concentrations in pus, as well as oxygen-derived free radicals [25,41] appear to be involved in the generation of brain edema in vitro and in vivo.…”

Diffusion-Weighted Magnetic Resonance Imaging of Acute Focal Cerebral Ischemia: Comparison of Signal Intensity with Changes in Brain Water and Na+,K+ -ATPase Activity

“…Cortex and basal ganglia specimens from the MCA territory were an alyzed separately. The water content (%) was measured and calculated as described by Chan et al (1983a).…”