Neurosteroids and epilepsy

Purpose of reviewNeurosteroids are a family of compounds synthesized directly in the brain bytransforming cholesterol into pregnenolone, which is then converted to compoundssuch as allopregnanolone and allotetrahydrodeoxycorticosterone. In view of their abilityto modulate neurotransmission, neurosteroids may influence the clinical course ofepileptic disorders. In this review, we highlight two emerging properties ofneurosteroids, that is, their anticonvulsant and antiepileptogenic activities.Recent findingsIt has been shown that fluctuations in neurosteroid synthesis, such as those seen inresponse to stress or during the ovarian cycle, determine an increase in seizurethreshold. Moreover, increased neurosteroid synthesis, presumably occurring in glialcells during epileptogenesis, delays the appearance of recurrent spontaneous seizuresin an animal model of temporal lobe epilepsy; such an effect may be due to augmentedtonic g-aminobutyric acid type A receptor-mediated inhibition. Finally, clinical trials withganaxolone, an allopregnanolone analogue, have demonstrated beneficial effects inpharmacoresistant epileptic patients, whereas finasteride – which interferes withneurosteroid synthesis – facilitates seizures in catamenial epilepsy.SummaryThe overall evidence suggests that neurosteroids may represent a novel therapeuticstrategy in epileptic disorders and a future perspective to control epileptogenicity.