Source: Northwestern University
A class of drug that inhibits estrogen production and is used to treat breast cancer has been found to quickly and effectively suppress dangerous brain seizures, according to a new Northwestern University study.
“The effect was profound and very clear,” said Catherine S. Woolley, Ph.D., senior author of the study, which was conducted in a rat model of status epilepticus, a condition characterized by a prolonged episode of seizure activity. “This shows that clinically available drugs could be effective therapies for suppressing seizures in humans.”
Woolley and postdoctoral fellow Satoru M. Sato also discovered, to their surprise, that seizures stimulate the production of estrogens in the brain of both males and females and that this plays a previously unknown role in the escalation of seizure activity. Estrogen synthesis during a seizure fuels the seizure, making it worse.
The findings suggest a new approach to treating seizures in humans: shut down the brain’s production of estrogen when a seizure first begins. Current seizure treatments are not targeted; they work by dampening neural activity generally and come with many side effects, such as drowsiness, dizziness or difficulty concentrating.
“Status epilepticus is a neurological emergency,” Woolley said. “This occurs when large groups of connected neurons fire excessively and in synchrony for a prolonged time. Recognizing that estrogen synthesis during seizures fuels seizure activity gives researchers a specific target for therapeutically breaking the dangerous escalation cycle.”
Woolley is the William Deering Chair in Biological Sciences, professor of neurobiology in the Weinberg College of Arts and Sciences and a member of the Women’s Health Research Institute at Northwestern University Feinberg School of Medicine.
The study, published as a research article by the online life sciences and biomedicine journal eLife, builds on past work showing estrogen increases neuronal activity via a number of mechanisms.
In their study, Woolley and Sato found inhibiting estrogen synthesis just after seizure onset strongly suppressed seizures in both sexes, without anti-seizure drugs or other interventions. The effect was seen both in the animal’s behavior and in hippocampal electroencephalogram (EEG) recordings.
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