Authors :
Presenting Author: Nicole Pinzon-Hoyos, M.S. – Southern Methodist University
Yibo Li, M.S. – Southern Methodist University
Kristin Boccardi, B.S. – Southern Methodist University
Amy Brewster, Ph.D. – Southern Methodist University
Rationale:
Epidemiological data reveal sex-based differences in epilepsy prevalence and clinical presentation. Males have higher overall epilepsy incidence and greater risk of injury-related epilepsy, while females more often exhibit idiopathic generalized epilepsy and more adverse effects from anti-seizure drugs. These disparities highlight the need to investigate sex-specific mechanisms. Recent studies show distinct brain transcriptomic and proteomic profiles between sexes in humans and rodents with epilepsy, suggesting sex-specific pathways in epileptic network development. Additionally, immune responses, both central and peripheral, appear to differ by sex in patients with refractory epilepsy and rodent models of status epilepticus (SE). Epilepsy patient data reveal sex-related imbalances in circulating complement and cytokine levels, while in response to SE, males show stronger hippocampal inflammation. However, the impact of these immune differences on seizure severity and behavior remains unclear. Therefore, this study aims to characterize immune responses along with behavioral deficits following SE in adult male and female rats.Methods:
Adult male and female rats underwent pilocarpine-induced SE (300 mg/kg, i.p.) for 1 hour, interrupted with diazepam (10 mg/kg, i.p.); controls received saline. Body weight was logged daily for 3 weeks. At 3 weeks post-SE (epileptogenesis), anxiety-like behavior and locomotion were assessed in the open field test. Then, hippocampi were collected for Western blot and multiplex ELISA to quantify the immune molecules: complement C3b, microglial TREM2, and cytokine levels.Results:
Following SE, male rats lost weight but recovered to control levels by 3 weeks, while females regained lost weight by day 4 and subsequently surpassed control weights thereafter. During epileptogenesis, SE females showed increased locomotor activity (distance and speed, p < 0.05) in the open field test, whereas SE males spent more time in the center of the arena (p< 0.05), indicating altered anxiety-related behavior. At 3 weeks post-SE, hippocampal cytokines (GM-CSF, IFN-γ, IL-2, IL-5, IL-10, TNF-α) were reduced in both sexes (p < 0.05), while complement C3b was elevated in both SE males and females compared to their respective controls. Trem2 protein levels were increased in SE males (p < 0.05) but unchanged in SE females (p > 0.05) compared to controls. Conversely, soluble Trem2 was elevated in SE females (p < 0.05) but not in SE males.