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Anti‐inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFβ1 regulation
Author(s) -
Stienen Martin N,
Haghikia Aiden,
Dambach Hannes,
Thöne Jan,
Wiemann Martin,
Gold Ralf,
Chan Andrew,
Dermietzel Rolf,
Faustmann Pedro M.,
Hinkerohe Daniel,
Prochnow Nora
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01038.x
Subject(s) - levetiracetam , astrocyte , electrophysiology , neuroscience , microglia , anticonvulsant , epilepsy , pharmacology , neuroglia , inflammation , neuroinflammation , medicine , biology , immunology , central nervous system
BACKGROUND AND PURPOSE The involvement of astrocytes as immune‐competent players in inflammation and the pathogenesis of epilepsy and seizure‐induced brain damage has recently been recognized. In clinical trials and practice, levetiracetam (LEV) has proven to be an effective antiepileptic drug (AED) in various forms of epileptic seizures, when applied as mono‐ or added therapy. Little is known about the mechanism(s) of action of LEV. Evidence so far suggests a mode of action different from that of classical AEDs. We have shown that LEV restored functional gap junction coupling and basic membrane properties in an astrocytic inflammatory model in vitro . EXPERIMENTAL APPROACH Here, we used neonatal rat astrocytes co‐cultured with high proportions (30%) of activated microglia or treated with the pro‐inflammatory cytokine interleukin‐1β to provoke inflammatory responses. Effects of LEV (50 µg·mL −1 ) on electrophysiological properties of astrocytes (by whole cell patch clamp) and on secretion of TGFβ1 (by elisa ) were studied in these co‐cultures. KEY RESULTS LEV restored impaired astrocyte membrane resting potentials via modification of inward and outward rectifier currents, and promoted TGFβ1 expression in inflammatory and control co‐cultures. Furthermore, LEV and TGFβ1 exhibited similar facilitating effects on the generation of astrocyte voltage‐gated currents in inflammatory co‐cultures and the effects of LEV were prevented by antibody to TGFβ1. CONCLUSIONS AND IMPLICATIONS Our data suggest that LEV is likely to reduce the harmful spread of excitation elicited by seizure events within the astro‐glial functional syncytium, with stabilizing consequences for neuronal–glial interactions.