Brivaracetam exhibits mild pro-inflammatory features in an \(\textit {in vitro}\) astrocyte-microglia co-culture model of inflammation
- Implications of glia in the pathophysiology of epilepsy raise the question of how these cells besides neurons are responsive to antiseizure medications (ASMs). Understanding ASM effects on glia and glia-mediated inflammation may help to explore astrocytes and microglia as potential targets for alternative anti-epileptogenic therapies. The aim of this study was to investigate the effects of the new generation ASM brivaracetam (BRV) in an astrocyte-microglia co-culture model of inflammation. Primary rat astrocytes co-cultures containing 5%–10% (M5, "physiological" conditions) or 30%–40% (M30, "pathological inflammatory" conditions) of microglia were treated with different concentrations of BRV (0.5, 2, 10, and 20 \(\mu\)g/ml) for 24 h. Glial cell viability was measured by MTT assay. Microglial activation states were analyzed by immunocytochemistry and astroglial connexin 43 (Cx43) expression by Western blot analysis and immunocytochemistry. Gap-junctional coupling was studied \(\it via\) Scrape Loading. Incubation with high, overdose concentration (20 \(\mu\)g/ml) of BRV significantly reduced the glial cell viability under physiological conditions (\(\it p\) < 0.01: **). Treatment with BRV in therapeutic concentrations (0.5 and 2 \(\mu\)g/ml) reduced the resting microglia (\(\it p\) < 0.05: *) and increased the microglial activation under inflammatory conditions (\(\it p\) < 0.01: **). Astroglial Cx43 expression was not affected. The gap-junctional coupling significantly increased only by 0.5 \(\mu\)g/ml BRV under physiological conditions (\(\it p\) < 0.05: *). Our findings suggest mild pro-inflammatory, \(\textit {in vitro}\) features of BRV with regard to microglia morphology. BRV showed no effects on Cx43 expression and only limited effects on gap-junctional coupling. Reduction of glial viability by overdose BRV indicates possible toxic effects.
Author: | Fatme Seval IsmailORCiDGND, Pedro FaustmannORCiDGND, Marie-Luise KümmelGND, Eckart FörsterORCiDGND, Timo Jendrik FaustmannORCiDGND, Franco CorvaceGND |
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URN: | urn:nbn:de:hbz:294-103649 |
DOI: | https://doi.org/10.3389/fncel.2022.995861 |
Parent Title (English): | Frontiers in cellular neuroscience |
Publisher: | Frontiers Research Foundation |
Place of publication: | Lausanne, Schweiz |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/11/10 |
Date of first Publication: | 2022/11/03 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds astrocyte-microglia co-culture model; brivaracetam; connexin 43; gap junctions; inflammation; toxicity |
Volume: | 16 |
Issue: | Article 995861 |
First Page: | 995861-1 |
Last Page: | 995861-15 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Knappschaftskrankenhaus Bochum, Klinik für Neurologie |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |