Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model
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.
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Animal experimentation: All animal procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Northwestern University Animal Care and Use Committee. Animal Study Protocol IS00000520 (expires 6/26/2017)Animal Welfare Assurance A3283-01
- Gary L Westbrook, Vollum Institute, United States
- Received: November 8, 2015
- Accepted: April 11, 2016
- Accepted Manuscript published: April 15, 2016 (version 1)
- Accepted Manuscript updated: April 18, 2016 (version 2)
- Version of Record published: May 10, 2016 (version 3)
- Version of Record updated: July 1, 2016 (version 4)
© 2016, Sato & Woolley
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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