Effect of Low Mg2+and Bicuculline on Cell Survival in Hippocampal Slice Cultures

A reliable model system of epileptiform insult would facilitate investigation into the underlying biological mechanisms. Epileptiform insult was induced in hippocampal slice cultures by lowering extracellular Mg2+, (+)-bicuculline, or (−)-bicuculline methochloride, a stable salt form of bicuculline (both forms block GABAA receptors). Cell death was assessed by propidium iodide uptake. Low Mg2+ or (+)-bicuculline did not produce cell death regardless of dose or incubation period. Exposure to 100 μM (−)-bicuculline methochloride for 48 hr resulted in prominent CA1 cell death. These findings demonstrate that not all pro-epileptic drugs/ion changes used routinely for electrophysiological recording of seizure activity lead to cell death in hippocampal slice cultures and that treatment with bicuculline methochloride can be used as a reliable model for epileptiform insult.