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• W4377965880 abstract "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.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.No differences in seizure susceptibility or mortality were observed between control males and control females. ORX males exhibited increased susceptibility and reduced latency to both GS and SE, but OVX females exhibited increased susceptibility and reduced latency to SE only. However, ORX males, but not OVX females, exhibited strongly increased seizure-induced mortality.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." @default.
• W4377965880 created "2023-05-25" @default.
• W4377965880 creator A5050760272 @default.
• W4377965880 creator A5084328103 @default.
• W4377965880 creator A5092007510 @default.
• W4377965880 date "2023-05-24" @default.
• W4377965880 modified "2023-09-27" @default.
• W4377965880 title "Sex and gonadectomy modify behavioral seizure susceptibility and mortality in a repeated low-dose kainic acid systemic injection paradigm in mice" @default.
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• W4377965880 doi "https://doi.org/10.1101/2023.05.22.541824" @default.
• W4377965880 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37292790" @default.
• W4377965880 hasPublicationYear "2023" @default.
• W4377965880 type Work @default.
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• W4377965880 hasAuthorship W4377965880A5050760272 @default.
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• W4377965880 hasAuthorship W4377965880A5092007510 @default.
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