科研之友
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摘要
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-1 beta to provoke inflammatory responses. Effects of LEV (50 mu g center dot mL-1) on electrophysiological properties of astrocytes (by whole cell patch clamp) and on secretion of TGF beta 1 (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 TGF beta 1 expression in inflammatory and control co-cultures. Furthermore, LEV and TGF beta 1 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 TGF beta 1.
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.
- 出版日期2011-1
