title: Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model.
abstract: Status epilepticus (SE) is a common neurological emergency for which new treatments are needed. In vitro studies suggest a novel approach to controlling seizures in SE: acute inhibition of estrogen synthesis in the brain. Here, we show in rats that systemic administration of an aromatase (estrogen synthase) inhibitor after seizure onset strongly suppresses both electrographic and behavioral seizures induced by kainic acid (KA). We found that KA-induced SE stimulates synthesis of estradiol (E2) in the hippocampus, a brain region commonly involved in seizures and where E2 is known to acutely promote neural activity. Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE.
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, United States.
authors.forename: Satoru M
authors.initials: SM
authors.lastname: Sato
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, United States.
authors.forename: Catherine S
authors.identifier: 0000-0002-8069-2646
authors.initials: CS
authors.lastname: Woolley
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects; D007266:Inhibition, Psychological; D007608:Kainic Acid / Q000008:administration & dosage; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D018377:Neurotransmitter Agents; D004958:Estradiol; D007608:Kainic Acid
keywords: estradiol; hippocampus; kainic acid; microdialysis; neuroscience; rat; seizure