Release of arachidonic acid (AA) is a neurotoxic mechanism of oxidative nature in trauma and ischemia. We studied ebselen effects on AA and 4-hydroxynonenal toxicity in rat cortical neurons in simulated ischemia in vitro by assessing cell viability and glutathione concentration. Ebselen normalized neuronal viability diminished by AA and 4-hydroxynonenal and increased glutathione level in normoxia and ischemia. AA elevated the glutathione level by 52 and 14% and 4-hydroxynonenal by 63 and 39% in normoxia and ischemia, respectively. Ebselen augmented the effect of AA in normoxia and diminished it in ischemia. Effect of 4-hydroxynonenal was similarly modulated by ebselen.