Mechanisms of arachidonic acid induced glial swelling

Accumulation of arachidonic acid (AA) in the brain during ischaemia may contribute to development of brain oedema. In this study we investigated the effect of selected drugs on AA-induced cytotoxic brain oedema in C6 glioma cells. Suspended C6 glioma cells were preincubated with drugs and AA (0.1 mM) was added. When no drug was administered cell volume increased immediately after the addition of AA with a maximum cell swelling of 13.1+/-1.9% at 15 min (mean +/- S.E. M.). Preincubation of cells with BW 755C, a dual inhibitor of cyclo- and lipoxygenases, showed no reduction in cell swelling from AA, whereas superoxide dismutase, amiloride and the protein kinase inhibitor H-9370 led to a significant attenuation of volume increase (p<0.05). The role of Na(+) ions during cell swelling from AA was evaluated after pretreatment of C6 glioma cells with ouabain. This resulted in a reversal of cell swelling (p<0.01). We conclude that there is potential involvement of free radicals, signal transduction systems and intracellular accumulation of Na(+) ions in glial cell swelling from AA.