title: Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.
abstract: In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the menstrual cycle. Many studies suggest that catamenial seizures are caused by fluctuations in gonadal hormones during the menstrual cycle, but this has been difficult to study in rodent models of epilepsy because the ovarian cycle in rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when epilepsy is severe, estrous cycles become irregular or stop. Therefore, we modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models of epilepsy so that seizures were rare for the first months after SE, and conducted video-EEG during this time. The results showed that interictal spikes (IIS) occurred intermittently. All rats with regular 4-day estrous cycles had IIS that waxed and waned with the estrous cycle. The association between the estrous cycle and IIS was strong: if the estrous cycles became irregular transiently, IIS frequency also became irregular, and when the estrous cycle resumed its 4-day pattern, IIS frequency did also. Furthermore, when rats were ovariectomized, or males were recorded, IIS frequency did not show a 4-day pattern. Systemic administration of an estrogen receptor antagonist stopped the estrous cycle transiently, accompanied by transient irregularity of the IIS pattern. Eventually all animals developed severe, frequent seizures and at that time both the estrous cycle and the IIS became irregular. We conclude that the estrous cycle entrains IIS in the modified KA and pilocarpine SE models of epilepsy. The data suggest that the ovarian cycle influences more aspects of epilepsy than seizure susceptibility.
authors: The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA; Cantonal Hospital of Basel, Land Institute of Pathology, Mühlemattstrasse 11, CH-4410 Liestal, Switzerland; Sackler Program in Biomedical Sciences, New York University Langone Medical Center, 550 First Ave., New York, NY 10016, USA.
authors: James
authors: J
authors: D'Amour
authors: Cantonal Hospital of Basel, Land Institute of Pathology, Mühlemattstrasse 11, CH-4410 Liestal, Switzerland.
authors: Alejandra
authors: A
authors: Magagna-Poveda
authors: The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA.
authors: Jillian
authors: J
authors: Moretto
authors: The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA; Comprehensive Epilepsy Center, New York University Langone Medical Center, 334 34th St., New York, NY 10016, USA.
authors: Daniel
authors: D
authors: Friedman
authors: The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA.
authors: John J
authors: JJ
authors: LaFrancois
authors: Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors: Patrice
authors: P
authors: Pearce
authors: Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA.
authors: Andre A
authors: AA
authors: Fenton
authors: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Rd, Guelph, ON N1G 2W1, Canada.
authors: Neil J
authors: NJ
authors: MacLusky
authors: The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA; Department of Child & Adolescent Psychiatry, Physiology & Neuroscience, and Psychiatry, New York University Langone Medical Center, One Park Ave, New York, NY 10016, USA. Electronic address: hscharfman@nki.rfmh.org.
authors: Helen E
authors: HE
authors: Scharfman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008597:Menstrual Cycle / Q000187:drug effects*; D010862:Pilocarpine / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D010862:Pilocarpine; D007608:Kainic Acid
keywords: Animal model; Epilepsy; Hormone; Kainic acid; Neuropathology; Seizure; Women