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Updated: Sep 10, 2025
Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Microglial activation is inhibited by selective anti-seizure medications
Robert Jürgen Platow1,2, Sabrina Pommer1,2,3,4,5, Julia Brauer1,2
1Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Objective:
To investigate the anti-inflammatory properties of anti-seizure medications (ASMs) administered to patients with drug-resistant epilepsy (DRE) and the role of sodium channels in microglial activation.
Material:
Primary microglia monocultures from mice brains.
Treatment:
Microglia were activated with 10 μg/mL lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) and pre- (45 min ASM then 2 h ASM plus stimulus) or post- (2 h stimulus then 24 h only ASM) treated with ASMs. Microglia were treated with cannabidiol (10 μM), stiripentol (250 μM), fenfluramine (50 μM), phenytoin (8 and 40 μM), cenobamate (300 and 900 μM), or the small molecule sodium channel blocker GS967 (10 and 30 μM). The sodium channel modulators tetrodotoxin (1 μM), µ-conotoxin KIIIA (1 μM), and β-pompilidotoxin (0.5 μM) were also applied.
Methods:
Microglia activation was quantified through measurements of Ptgs2 (Cox2), Tnf-α, and Ifn-β induction by RT-qPCR and of cell morphology by immunocytochemistry. Expression of sodium channels in microglia was studied using PCR, RT-qPCR, immunohisto- and immunocytochemistry. Mann Whitney test and the Kruskal-Wallis test with Dunn's multiple comparisons post-test were used.
Results:
ASMs have a differential effect on microglial activation. Uniquely, cenobamate inhibited the induction of Ifn-β and made the cells less amoeboid. The voltage gated sodium channel Nav1.2 is expressed by microglial cells and its expression levels change with microglial inflammatory response. Toxins that block sodium channels modulated microglial activation.
Conclusions:
ASMs, applied to patients with DRE, have a differential ability to reduce microglial activation and pro-inflammatory microglial morphology in vitro. Moreover, sodium channel blockage modulates inflammation through microglia activation. Taken together these results suggest, that further investigation of patient's immune response to ASMs could be important.
Insights
Anti-seizure medications (ASMs) differentially impact microglial activation in drug-resistant epilepsy models. Sodium channel blockers modulate this inflammation, suggesting ASMs may influence immune responses in patients.
Area of Science:
- Neuroimmunology
- Pharmacology
- Epilepsy Research
Background:
- Drug-resistant epilepsy (DRE) presents significant treatment challenges.
- Microglia play a crucial role in neuroinflammation, which is implicated in epilepsy.
- The anti-inflammatory properties of anti-seizure medications (ASMs) are not fully understood.
Purpose of the Study:
- To investigate the anti-inflammatory effects of ASMs on microglial activation.
- To explore the role of sodium channels in microglial inflammatory responses.
- To assess the impact of ASMs on pro-inflammatory microglial morphology.
Main Methods:
- Primary mouse microglia monocultures were activated using lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C).
- Microglia were treated with various ASMs (e.g., cenobamate, phenytoin) and sodium channel blockers (e.g., GS967, tetrodotoxin).
- Microglial activation was quantified via RT-qPCR (Ptgs2, Tnf-α, Ifn-β) and immunocytochemistry; sodium channel expression was also analyzed.
Main Results:
- ASMs demonstrated differential effects on microglial activation.
- Cenobamate uniquely inhibited interferon-beta (Ifn-β) induction and reduced amoeboid morphology.
- Voltage-gated sodium channel Nav1.2 was expressed in microglia, and its levels correlated with inflammatory responses; sodium channel blockers modulated microglial activation.
Conclusions:
- ASMs exhibit varying capacities to reduce in vitro microglial activation and pro-inflammatory morphology.
- Sodium channel blockade influences inflammation via microglial activation pathways.
- Further research into patient immune responses to ASMs is warranted.
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