Anti-Seizure Medications and Estradiol for Neuroprotection in Epilepsy: The 2013 Update
Libor Velisek, Nino Nebieridze, Tamar Chachua and Jana Veliskova
Affiliation: New York Medical College, Department of Cell Biology & Anatomy, BSB-A20, 40 Sunshine Cottage Rd. Valhalla, NY 10595, USA.
Current epilepsy therapy is still symptomatic using anti-seizure, rather than anti-epileptic, medications. This
therapy may control the seizure activity but does not prevent or even cure epilepsy. Treatment strategies that could interfere
with the process leading to epilepsy (epileptogenesis) would have significant benefits over the current approaches.
Neuronal damage contributing to remodeling of the neuronal networks (such as in the hippocampus during temporal lobe
epilepsy) is one of the significant components of ongoing epileptogenesis. Thus, treatment strategies alleviating seizureinduced
neuronal damage and network reorganization may become powerful tools fighting the deteriorating process of
epileptogenesis. Current anti-seizure medications, especially valproic acid, have some neuroprotective potential. Similarly,
there is some hope of neuroprotection with newer anti-seizure drugs such as retigabine and levetiracetam. However,
the neuroprotective potential of anti-seizure medications is frequently weak or masked by negative side effects associated
with long-term treatment, therefore exceeding the benefits.. Thus, the attention is shifted to different compounds with already
established neuroprotective potential. Among steroid hormones under investigation, two groups appear interesting:
β-estradiol and selective estrogen receptor modulators – SERM. In low doses, β-estradiol has neuroprotective potency in
neurodegenerative diseases. However, its use for seizure-induced neuroprotection is confounded by a common perception
of proconvulsant features of estrogens. Here we review that both features, effects on neuronal excitability and neuroprotection,
apply under specific conditions and may be separated by individualized therapy taking into account the dosage
paradigm, timing, sex and age of the subjects and their gonadal hormone status (including progesterone: opposed vs. unopposed
estrogen). Several studies have demonstrated that β-estradiol has indeed potency to protect neurons from seizureinduced
damage. Additional studies are required to determine exact mechanisms of β-estradiol and SERMs in seizureinduced
neuroprotection for truly individualized and effective therapy. The article presents some promising patents on
Keywords: Anti-seizure medications, estrogen, genomic effects, non-genomic effects, neuronal damage, status epilepticus.
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