Authors :
Presenting Author: Zahra Sadri, MA – Southern Methodist University
yibo li, MS – Southern Methodist University
Surabhi Soni, BS – Southern Methodist University
Ashiyana Dahiya, BS – Southern Methodist University
AMY.L Brewster, PhD – Southern Methodist University
Rationale:
Microglia are essential for brain health and disease response. In the healthy brain, they continuously survey the parenchyma, enabling rapid inflammatory and phagocytic responses to immune challenges and homeostatic disruptions. Under seizure conditions, microglia adopt reactive phenotypes marked by changes in surveillance, inflammation, and phagocytosis. The microglial receptor TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) can regulate survival, inflammation, and phagocytosis, but its role in epilepsy remains unclear. We previously observed reduced TREM2 and sex-specific signaling in human epilepsy brain biopsies. Therefore, this study aims to determine how microglial TREM2 loss affects hippocampal neuroinflammatory responses after status epilepticus (SE), focusing on sex-specific effects. To test this, we used the pilocarpine-induced SE mouse model of acquired epilepsy and examined behavioral and electrographic seizures along with acute hippocampal inflammation.Methods:
Adult female and male TREM2KO and C57BL/6J (wild type; WT) mice were implanted with cortical electrodes and video-EEG recorded for baseline electrographic activity for 2 weeks. To induce SE, mice received pilocarpine (300 mg/kg, i.p.), or saline (controls). Groups included males (M) and females (F): WT controls (C), WT-SE, TREM2 KO-C, and TREM2 KO-SE, n = 4-7/group. Video-EEG and Racine scales were used to monitor/score seizure activity. After one hour of SE, mice were transcardially perfused with saline, and hippocampi were collected for histological and biochemical analyses. EEG traces were analyzed for seizure onset time, duration, severity, and total spectral power (0–70 Hz). Neuronal activation was assessed via P-S6 immunoreactivity (mTOR marker), and ELISAs measured the inflammatory cytokines IL-6, TNFα, and IL-1β.
Results:
Comparisons of EEG analyses of SE groups by sex (M vs. F) and genotype (WT vs. TREM2 KO) revealed no significant differences (p > 0.05, ANOVA) in electrographic epileptiform activity or total spectral power (0–70 Hz), indicating similar seizure severity in all mice. At 1 hour of SE, robust P-S6 immunoreactivity was observed in all SE groups compared to respective sex- and genotype-matched controls. ELISA revealed elevated IL-6 in male WT-SE mice compared to WT-C males (p < 0.05). In contrast, IL-6 levels were not elevated in TREM2 KO-SE males compared to TREM2 KO controls. TNFα and IL-1β levels remained unchanged across groups in response to SE.