Loss of GABAergic interneurons contributes to the development of spontaneous seizures in severe human temporal lobe epilepsy (TLE) and in rodent models of TLE. We study the mechanisms of neuronal cell death in epilepsy and neural circuit repair with stem cell grafts. We are developing strategies for long-term cell-based repair of limbic system damage in TLE and examining seizure suppression by transplants of GABAergic interneuron progenitors. Our work utilizes mouse models of TLE including kainic acid and pilocarpine models. We are using mouse and human embryonic stem cell derived progenitors, as well as fetus-derived GABAergic precursors from the embryonic forebrain and evaluating their efficacy for suppressing spontaneous recurrent seizures in the pilocarpine model of TLE. We also study the link between DNA damage, intracellular signaling involving BAX, and excitotoxic cell death. Our research employs in vitro studies of neurons as well as in vivo cellular, molecular and electrophysiological studies with transgenic and knockout mice, focusing on the hippocampus and cerebral cortex.
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