Arachidonic acid and its metabolites are released in brain extracellular fluids as a result of ischemia and may participate in either damaging or protecting neural tissues. This study investigates the neuroprotective effect of prostacyclin (PGI2) on hypoxia (5 h)/reoxygenation (3 h) and on the excitotoxic neurotransmitter, glutamate (10 microM), in rat cortical neuron cultures. At microM concentrations, PGI2 inhibits lactate dehydrogenase release, a cell-injury marker. These results, showing a direct cytoprotective effect of PGI2 on brain cells, reinforce its beneficial properties on vessels and circulating cells in cerebral ischemia.