Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes

There is accumulating evidence that epileptic activity is accompanied by inflammatory processes. In the present study, we evaluated the effect of levetiracetam (Keppra), an anticonvulsant drug with decisive antiepileptic features, with regard to its putative antiinflammatory potential. We previously established an in vitro cell culture model to mimic inflammatory conditions: Primary astrocytic cultures of newborn rats were cocultured with 30% (M30) microglial cells. Alternatively, co-cultures containing 5% microglia (M5) were incubated with the proinflammatory mediator, the cytokine interleukin-1 beta (IL-1 beta), and lipopolysaccharide (LPS), a potent bacterial activator of the immune system. For the M30 cocultures, we observed reduced expression of connexin 43 (Cx43), the predominant gap junction protein. Impaired functional dye coupling and depolarized membrane resting potential (MRP) were monitored in M30 cocultures as well as in M5 cocultures treated with IL-1 beta and LPS. We could show that the Cx43 expression, the coupling property, and the membrane resting potential on which we focused our inflammatory coculture model were normalized to noninflammatory level under treatment with levetiracetam (Keppra). Cumulatively, our results provide evidence for antiinflammatory properties of levetiracetam in seizure treatment. (c) 2008 Wiley-Liss, Inc.