Impact of Dysbiosis and Antiseizure Medication on Acute and Chronic Seizure Neuropathology in a Viral-Induced Epilepsy Model
Abstract number :
1.11
Submission category :
14. Neuropathology of Epilepsy
Year :
2025
Submission ID :
92
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Sophia Shonka, PhD – University of Washington
Inga Erickson, MS – University of Washington
Hannah Park, BS – University of Washington
Melissa Barker-Haliski, PhD – University of Washington
Rationale: Viral infections are major contributors to acute symptomatic seizure (ASyS) development and epileptogenesis. In mice, the Theiler’s murine encephalomyelitis virus (TMEV) is used to mimic the CNS infection disease trajectory observed clinically. CNS infection is linked to epilepsy due to the inflammatory cytokine cascade that subsequently induces neuronal hyperexcitability, thereby contributing to acute neuropathology and later epileptogenesis. Interestingly, inflammation both within and outside the CNS contributes to ASyS onset. The gut microbiome is an underexplored contributor to CNS inflammation but may significantly influence epileptogenesis and antiseizure medication (ASM) efficacy. We thus hypothesized that antibiotic (ABX)-induced dysbiosis would alter acute and chronic neuropathology following TMEV infection-induced ASyS, reflecting a disease-modifying contribution of the gut microbiome on epilepsy.
Methods: Male C56BL/6J mice (4-5 weeks old) were given oral antibiotics (ABX) or saline (SAL) and infected with TMEV. Next, carbamazepine (CBZ; 20 mg/kg) or vehicle (VEH; 0.5% methylcellulose) was administered during the acute infection period. Chronic histopathology was then assessed in mice 5-6 weeks after TMEV infection. Mice were euthanized, and histopathology performed on hippocampal tissue to assess cell death, microgliosis, astrogliosis, and neuron proliferation.
Results: Following acute TMEV infection, we found significant pathology in the hippocampal CA1 and CA3 regions. In CA1, microgliosis was impacted (F(1,29)=9.257, p< 0.01) with SAL-CBZ mice displaying more microgliosis than ABX-VEH (p< 0.05) and SAL-VEH mice (p< 0.05). Neurodegeneration further impacted microgliosis (F(4,21)=13.37, p< 0.0001, Adj. R2=0.66) whereby SAL-CBZ mice displayed a positive correlation (β=0.83, p< 0.001), especially versus the ABX-VEH group (p< 0.001). In CA3, seizure burden impacted neurodegeneration (F(4,21)=3.966, p< 0.05, Adj. R2=0.32) with positive correlations for SAL-VEH (β=4.14, p< 0.05) and ABX-CBZ (
Neuropathology of Epilepsy