Castration in female rats modifies the development of the pilocarpine model of epilepsy

Valente, Sandra Gomes; Naffah-Mazzacoratti, Maria da Graça; Pereira, M; Silva, I; Santos, Nuno M.S. dos; Baracat, Edmund Chada; Cavalheiro, Ésper A.; Amado, Débora

doi:10.1016/s0920-1211(02)00024-4

Cited by 24 publications

(31 citation statements)

References 30 publications

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“…When these chronically induced epileptic female rats were mated, it was possible to observe a decrease in the frequency of spontaneous seizures during pregnancy and lactation (Amado and Cavalheiro 1998). As previously described by Valente et al (2002), the castration in female rats decreased the latency for pilocarpine-induced SE, increased the SErelated mortality and decreased the latent period to spontaneous seizures.…”

Section: Hormonal Changes Related To Epilepsysupporting

confidence: 75%

“…So, as it was seen by Valente et al (2002), the castrated epileptic female rats present a more intense grade of mossy fiber sprouting in comparison to intact epileptic animals ( Fig. 2A).…”

Section: Hormonal Changes Related To Epilepsysupporting

confidence: 62%

“…However, there are controversies regarding the hippocampal damage, which concerns if it is a cause or consequence of seizures. This point is interesting because, in this study and in that previous study of Valente et al (2002), we demonstrated that the castrated epileptic animals presented a more intense grade of sprouting compared to that showed in non-castrated epileptic animals, and the frequency seizures in both groups did not show any differences. Mathern et al (1995Mathern et al ( , 1996 did not find a correlation between the mossy fiber sprouting and seizure frequency, and only correlated the density of sprouting (in animals and human) with neuronal loss in the hilus of dentate gyrus.…”

Section: Hormonal Changes Related To Epilepsysupporting

confidence: 62%

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The pilocarpine model of epilepsy: what have we learned?

Scorza

Arida

Naffah-Mazzacoratti

et al. 2009

An. Acad. Bras. Ciênc.

163

103

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The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioral and electrographic changes that can be divided into 3 distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behavior which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, the pilocarpine model of epilepsy is a valuable tool not only to study the pathogenesis of temporal lobe epilepsy in human condition, but also to evaluate potential antiepileptogenic drugs. This review concentrates on data from pilocarpine model of epilepsy.

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Section: Hormonal Changes Related To Epilepsysupporting

confidence: 75%

“…So, as it was seen by Valente et al (2002), the castrated epileptic female rats present a more intense grade of mossy fiber sprouting in comparison to intact epileptic animals ( Fig. 2A).…”

Section: Hormonal Changes Related To Epilepsysupporting

confidence: 62%

Section: Hormonal Changes Related To Epilepsysupporting

confidence: 62%

See 1 more Smart Citation

The pilocarpine model of epilepsy: what have we learned?

Scorza

Arida

Naffah-Mazzacoratti

et al. 2009

An. Acad. Bras. Ciênc.

163

103

View full text Add to dashboard Cite

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“…Numerous studies over the last few decades have identified sex and cycle-dependent differences in seizure susceptibility in rodents. These studies have used various methods to induce seizures, including kindling, electroshock, and chemoconvulsant administration Buterbaugh, 1989;Edwards et al, 1999;Finn and Gee, 1994;Hoffman et al, 2003;Hom and Buterbaugh, 1986;Hudson and Buterbaugh, 1991;Kalkbrenner and Standley, 2003;Matejovska et al, 1998;Nicoletti et al, 1985;Pericic and Bujas, 1997;Persinger et al, 1988;Pesce et al, 2000;Schwartz-Giblin et al, 1989;Slamberova and Vathy, 2000;Tan and Tan, 2001;Tominaga et al, 2001;Valente et al, 2002;Velisek et al, 1999;Wahnschaffe and Loscher, 1992;Woolley, 2000). However, these studies have failed to provide a clear picture of the relationship between ovarian hormone levels and seizure susceptibility.…”

Section: Introductionmentioning

confidence: 99%

“…Most studies have also focused on a few specific endpoints, without consideration of other potential factors that may contribute to seizure susceptibility. For example, in one recent study, susceptibility to pilocarpine-induced seizures was compared in ovariectomized and intact rats, but the intact rats only included animals at the estrous stage of the female reproductive cycle (the ''estrous cycle''; Valente et al, 2002). While ovariectomized animals appeared to have a shorter latency to seizures than intact rats, general conclusions regarding the role of the ovarian hormones could not be drawn, since other stages of the reproductive cycle were not included.…”

Section: Introductionmentioning

confidence: 99%

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

Scharfman

Goodman

Rigoulot

et al. 2005

Experimental Neurology

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Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00-10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpineinduced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures.

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Sex and gonadectomy modify behavioral seizure susceptibility and mortality in a repeated low‐dose kainic acid systemic injection paradigm in mice

Lawande,

Conklin,

Christian‐Hinman

2023

Epilepsia Open

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Objective:Sex differences in epilepsy appear driven in part due to effects of gonadal steroids, with varying results in experimental models based on species, strain, and method of seizure induction. Furthermore, removing a main source of these steroids via gonadectomy may impact seizure characteristics differently in males and females. Repeated low‐dose kainic acid (RLDKA) systemic injection paradigms were recently shown to reliably induce status epilepticus (SE) and hippocampal histopathology in C57BL/6J mice. Here, we investigated whether seizure susceptibility in a RLDKA injection protocol exhibits a sex difference, and whether gonadectomy differentially influences response to this seizure induction paradigm in males and females.Methods:Adult C57BL/6J mice were left gonad‐intact as controls or gonadectomized (females: ovariectomized, OVX; males: orchidectomized, ORX). At least 2 weeks later, KA was injected i.p. every 30 minutes at 7.5 mg/kg or less until the animal reached SE, defined by at least 5 generalized seizures (GS, Racine stage 3 or higher). Parameters of susceptibility to GS induction, SE development, and mortality rates were quantified.Results:No differences in seizure susceptibility or mortality were observed between control males and control females. Gonadectomized mice exhibited increased susceptibility and reduced latency to both GS and SE in comparison to corresponding controls of the same sex, but the effects were stronger in males. In addition, ORX males, but not OVX females, exhibited strongly increased seizure‐induced mortality.Significance:The RLDKA protocol is notable for its efficacy in inducing SE and seizure‐induced histopathology in C57BL/6J mice, the background for many transgenic strains in current use in epilepsy research. The present results indicate that this protocol may be beneficial for investigating the effects of gonadal hormone replacement on seizure susceptibility, mortality, and seizure‐induced histopathology, and that gonadectomy unmasks sex differences in susceptibility to seizures and mortality not observed in gonad‐intact controls.

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Castration in female rats modifies the development of the pilocarpine model of epilepsy

Cited by 24 publications

References 30 publications

The pilocarpine model of epilepsy: what have we learned?

The pilocarpine model of epilepsy: what have we learned?

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

Sex and gonadectomy modify behavioral seizure susceptibility and mortality in a repeated low‐dose kainic acid systemic injection paradigm in mice

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