A rat model of epilepsy in women: A tool to study physiological interactions between endocrine systems and seizures

Helen E. Scharfman, Gauri H. Malthankar-Phatak, Daniel Friedman, Patrice Pearce, Daniel P. McCloskey, Cynthia L. Harden, Neil J. MacLusky

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Epilepsy inwomenis influenced by endocrine status and antiepileptic drugs, but without an animal model, the effects of endocrine variables and antiepileptic drugs cannot be easily dissociated from the influence of epilepsy itself. Animal models have had limited utility because experimentally induced seizures typically result in reproductive failure. This study was conducted to develop an improved animal model. The muscarinic convulsant pilocarpine was used to elicit status epilepticus (SE) in adult female Sprague Dawley rats. The selective estrogen receptor modulator raloxifene was administered 30 min before pilocarpine. An anticonvulsant barbiturate, pentobarbital, was injected 5-10 min after the onset of SE and at least once thereafter to minimize acute convulsions. Mortality, morbidity, estrous cyclicity, and the ultimate success of the procedure (i.e. induction of recurrent, spontaneous seizures) were monitored. The combination of raloxifene and pentobarbital led to significantly improve destrous cyclicity compared with previous methods. Animals treated with raloxifene and pentobarbital became epileptic, as defined by the recurrence of spontaneous convulsions in the weeks after SE. The results of this study provide an improved animal model to examine the interactions between seizures and ovarian hormone secretion. The results also suggest that treatment of SE with raloxifene may benefit women with SE.

Original languageEnglish
Pages (from-to)4437-4442
Number of pages6
JournalEndocrinology
Volume150
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

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