Anti-inflammatory properties of lacosamide in an astrocyte-microglia co-culture model of inflammation

• Published in: European journal of pharmacology Vol. 915; p. 174696
• Main Authors: Corvace, Franco, Faustmann, Timo Jendrik, Faustmann, Pedro M., Ismail, Fatme Seval
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2022
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anticonvulsants - pharmacology; Astrocyte-microglia co-culture model; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Cell Communication - drug effects; Cell Survival - drug effects; Cells, Cultured; Coculture Techniques; Connexin 43 - metabolism; Gap junctions; Gap Junctions - drug effects; Gap Junctions - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Lacosamide; Lacosamide - pharmacology; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Rats; Rats, Wistar; Astrocyte-microglia co-culture model; Inflammation; Gap junctions; Lacosamide
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2021.174696

Understanding the effects of antiepileptic drugs on glial cells and glia-mediated inflammation is a new approach to future treatment of epilepsy. Little is known about direct effects of the antiepileptic drug lacosamide (LCM) on glial cells. Therefore, we aimed to study the LCM effects on glial viability, microglial activation, expression of gap-junctional (GJ) protein Cx43 as well as intercellular communication in an in vitro astrocyte-microglia co-culture model of inflammation. Primary rat astrocytes co-cultures containing 5% (M5, “physiological” conditions) or 30% (M30, “pathological inflammatory” conditions) of microglia were treated with different concentrations of LCM [5, 15, 30, and 90 μg/ml] for 24 h. Glial cell viability was measured by MTT assay. Immunocytochemistry was performed to analyze the microglial activation state. Western blot analysis was used to quantify the astroglial Cx43 expression. The GJ cell communication was studied via Scrape Loading. A concentration-dependent incubation with LCM did not affect the glial cell viability both under physiological and pathological conditions. LCM induced a significant concentration-dependent decrease of activated microglia with parallel increase of ramified microglia under pathological inflammatory conditions. This correlated with an increase in astroglial Cx43 expression. Nevertheless, the functional coupling via GJs was significantly reduced after incubation with LCM. LCM has not shown effects on the glial cell viability. The reduced GJ coupling by LCM could be related to its anti-epileptic activity. The anti-inflammatory glial features of LCM with inhibition of microglial activation under inflammatory conditions support beneficial role in epilepsy associated with neuroinflammation. •Anti-inflammatory glial features of lacosamide with inhibition of microglial activation under inflammatory conditions.•Lacosamide has not shown effects on the glial cell viability.•The reduced gap-junctional coupling by lacosamide can be related to its anti-epileptic activity.•Astrocytes-microglia co-culture model of inflammation allows to study the inflammatory reaction under antiepileptic drugs.