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Exp Neurol. 2015 Jul;269:102-19. doi: 10.1016/j.expneurol.2015.04.003. Epub 2015 Apr 10.

Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.

Author information

1
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.
2
Cantonal Hospital of Basel, Land Institute of Pathology, Mühlemattstrasse 11, CH-4410 Liestal, Switzerland.
3
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY 10962, USA.
4
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.
5
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
6
Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA.
7
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Rd, Guelph, ON N1G 2W1, Canada.
8
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.

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.

KEYWORDS:

Animal model; Epilepsy; Hormone; Kainic acid; Neuropathology; Seizure; Women

PMID:
25864929
PMCID:
PMC4446145
DOI:
10.1016/j.expneurol.2015.04.003
[Indexed for MEDLINE]
Free PMC Article

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