Epilepsy is a common and devastating neurological disease affecting more than 50 million people worldwide. Accumulating experimental and clinical evidence suggests that inflammatory pathways contribute to the development of
seizures in various forms of
epilepsy. In this context, while the activation of the
PGE2 EP2 receptor causes early neuroprotective and late neurotoxic effects, the role of EP2 receptor in
seizures remains unclear. We investigated whether the systemic administration of the highly selective EP2 agonist
ONO-AE1-259-01 prevented acute
pentylenetetrazole (PTZ)- and
pilocarpine-induced
seizures. The effect of
ONO-AE1-259-01 on cell death in the hippocampal formation of adult male mice seven days after
pilocarpine-induced
status epilepticus (SE) was also evaluated.
ONO-AE1-259-01 (10μg/kg, s.c.) attenuated PTZ- and
pilocarpine-induced
seizures, evidenced by the increased latency to
seizures, decreased number and duration of
seizures episodes and decreased mean amplitude of electrographic
seizures.
ONO-AE1-259-01 and
pilocarpine alone significantly increased the number of pyknotic cells per se in all hippocampal subfields. The EP2 agonist also additively increased
pilocarpine-induced pyknosis in the pyramidal cell layer of CA1 but reduced
pilocarpine-induced pyknosis in the granule cell layer of the dentate gyrus (DG). Although the systemic administration of
ONO-AE1-259-01 caused a significant
anticonvulsant effect in our assays, this EP2 agonist caused extensive cell death. These findings limit the likelihood of EP2 receptor agonists being considered as novel potential
anticonvulsant drugs.