Authors :
Hyo Jung Shin, PhD – Eulji University School of Medicine
In Soo Kim, MD, PhD – Chungnam National University College of Medicine
Minwoo Kim, MS – Chungnam National University College of Medicine
Seung Yeon Jung, MD – Chungnam National University Hospital
Dong Woon Kim, VMD, PhD – Kyung Hee University College of Dentistry
Presenting Author: Joon Won Kang, MD, PhD – Chungnam National University Hospital; Chungnam National University College of Medicine
Rationale:
This study aims to investigate the factors underlying the transition from the first seizure to a subsequent seizure, focusing on the characteristics of microglia in the development of epilepsy.
Methods:
Kainic acid (KA) was diluted in saline to a concentration of 100 μg/μl and injected intraperitoneally into C57BL6/J mice at a dose of 5 mg/kg every 20 min. Once seizures reached Racine stage 4/5, the administration was stopped, and the mice were monitored for 60 min. Only mice that exhibited behavioral status epilepticus (SE) in the first experiment underwent a second round of KA injections 2 weeks later. Using this model, we observed changes in brain tissue and microglial phenotypes based on seizure sensitivity. We analyzed the gene expression patterns related to microglial phagocytosis from a publicly available hippocampal transcriptome microarray dataset (GSE88992) of KA-injected mice. Additionally, we examined the immunofluorescence staining results of triggering receptor expressed on myeloid cells 2 (TREM2) and microglial outcomes in the brain tissues of the model.
Results:
Following the first round of low-dose KA repeated injections, status epilepticus (SE) was induced in 72 out of 78 mice (92.3%). During the second round of injections, the number of injections required to induce SE was compared to the first round, leading to the classification of mice into seizure resistance (SR, n=26), seizure tolerance (ST, n=11), and seizure susceptibility (SS, n=15) groups. While neuronal loss was observed in all seizure groups, its extent varied across different hippocampal regions. Notably, microglial phenotypes in the hippocampus exhibited significant differences between groups. Over time, genes associated with microglial activation, including TREM2, showed increased expression following KA injection into the hippocampus. Immunofluorescence staining further confirmed elevated TREM2 expression in microglia within the SS group.Conclusions:
This study highlights the role of microglia in the progression from the first to subsequent seizures, a critical step in the development of epilepsy. Using a model that classified seizure resistance, tolerance, and susceptibility, we observed significant differences in microglial phenotypes and TREM2 expression across groups. These findings indicate that TREM2 may serve as a key factor in epileptogenesis.
Funding:
This work was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT, Republic of Korea (RS-2022-NR069376).