Astrocytes and microglia have a role in the pathophysiology of epilepsy and bipolar illness, and their involvement is linked to inflammation. For a study, researchers sought to examine how the antiepileptic and mood-stabilizing drugs lamotrigine (LTG) and topiramate (TPM) affected glial viability, microglial activation, cytokine release, and expression of the gap-junctional protein connexin 43 (Cx43) in different configurations of an in vitro astrocyte-microglia co-culture model of inflammation.
For 24 hours, primary rat co-cultures of astrocytes containing 5% (M5, representing “physiological” circumstances) or 30% (M30, representing “pathological, inflammatory” conditions) of microglia were treated with various amounts of LTG and TPM. The glial cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Immunocytochemistry was used to examine the activation status of microglia. TNF-α (tumor necrosis factor-α) and TGF-ß1 (transforming growth factor-ß1) cytokine levels were evaluated using an enzyme-linked immunosorbent assay. The expression of Cx43 in astroglia was measured using a western blot.
Under all circumstances, glial cell viability was significantly reduced after incubation with LTG or TPM in a concentration-dependent manner. LTG had no discernible effect on microglial phenotypes. TPM reduces microglial activation in a concentration-dependent manner under pathogenic circumstances. It was linked to an increase in astroglial Cx43 expression. LTG and TPM had no effect on TNF- levels. Higher LTG concentrations, but not TPM, resulted in a considerable rise in TGF-ß1 levels in M5 and M30 co-cultures.
Despite the potential glial toxicity of LTG and TPM, both medicines lowered inflammatory activity, indicating potential beneficial effects on the neuroinflammatory components of epilepsy and bipolar disorder etiology.