The role of estrogens in seizures and epilepsy: the bad guys or the good guys?

Estrogens influence neuronal activity and are important for normal brain functions. Effects of estrogens on seizures are contradictory. It is commonly accepted that estrogens may increase neuronal excitability and thus mediate proconvulsant effects. However, clinical and animal data show that estrogen may also have no effect or anticonvulsant effects. The action of estrogens on seizures depends on various factors, such as treatment duration and latency prior to the seizure testing, estrogen dose, hormonal status (naïve vs gonadectomized animals), estrogenic substance, the region/neurotransmitter system involved, the seizure type/model used, and sex. Besides the effects on seizure susceptibility, estrogens may also play an important role in seizure-induced damage. Pretreatment with beta-estradiol in ovariectomized female rats has neuroprotective effects on status epilepticus-induced hippocampal damage and prevents the loss of inhibition in the dentate gyrus during the early post-status epilepticus period determined by the in vitro paired pulse paradigm. Several signaling pathways may be involved in the neuroprotective effects of beta-estradiol on status epilepticus-induced hippocampal damage but at least one of these pathways involves interactions with neuropeptide Y.