Epilepsy provoked by pentylenetetrazol (PTZ) is caused by an abnormal excitatory postsynaptic potential, which results in increased production of reactive oxygen species, and finally reducing cognitive functions. The objective of this study was to investigate the effects of dietary supplementation with DHA and PS, administered either alone or in combination, on oxidative stress and behavioral and cognitive spatial memory in neonatal rats with PTZ-induced epileptic seizure. In this study, rat pups received repetitive doses of PTZ for induction of epileptic seizure and docosahexaenoic acid (DHA, C22:6, n-3) and phosphatidylserine (PS) were orally administrated alone or together to the PTZ-induced epileptic animals daily for 36 d. The spatial memory, nitric mono-oxide (NO) production, and enzymatic activities of superoxide dismutase (SOD) and catalase in brain and liver tissues were determined. PTZ administration significantly reduced the cell numbers in the hippocampus, shortened the escape latency in the safe target region, decreased activities of SOD and catalase, but increased NO content in both brain and liver tissues, while DHA and PS significantly extended the escape latency, reversed the oxidative parameters observed in the brain, and enhanced SOD activity in the liver. Dietary supplementation with DHA and PS may protect brain tissue from the oxidative stress caused by epileptic seizures and could serve to improve learning and memory ability in vivo.

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