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

Purpose: 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 astrocytemicroglia co-culture model of inflammation. Methods: 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 mu g/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. Results: 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. Conclusion: 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.

Automated summary

This study investigated the effects of the antiepileptic drug lacosamide (LCM) on glial cells and found that LCM did not affect glial cell viability but inhibited microglial activation and increased astroglial Cx43 expression under inflammatory conditions.