Cell death and metabolic activity during epileptiform discharges and status epilepticus in the hippocampus

Mechanisms of seizure-induced cell death were studied in organotypic hippocampal slice cultures. These develop after withdrawal of magnesium recurrent seizure-like events (SLE), which lead to intracellular and intramitochondrial calcium accumulation. The intramitochondrial Ca accumulation seems to be involved in causing increased production of NADH, measured as NAD(P)H autofluorescence. During SLEs, depolarization of mitochondria and increased production of free radicals is indicated by fluorescence measurements with appropriate dyes. During recurrent seizures, an increased failure to produce NADH is noted while at the same time free radical production seems to increase. This increase and the decline in NADH production could be involved in transition to late recurrent discharges, a phase in which status epilepticus becomes pharmacoresistant. It also coincides with increased cell death as determined with propidium iodide fluorescence. Interestingly, some of these changes can be prevented by application of alpha-tocopherol, a free radical scavenger, which also has neuroprotective effects under our experimental conditions. The results suggest that free radical-induced mitochondrial impairment is involved in seizure-induced cell death.