Post-seizure drug treatment in young rats determines clear incremental losses of frontal cortical and hippocampal neurons: the resultant damage is similar to very old brains.

Loss of neurons occurs with aging and following lithium/pilocarpine-induced epileptic seizures. In the present study, the numbers of neurons within the layers from sample areas of the four lobes of the neocortices and the hippocampus were counted by light microscopy in brains of rats that had been administered lithium or pilocarpine and then injected immediately or shortly after seizure onset with either acepromazine, ketamine, or prazosin. The mean numbers of neocortical and hippocampal neurons were lowest in rats treated with acepromazine or prazosin 1h after seizure onset, while those of rats immediately treated with ketamine displayed the least decrements and were most similar to normal rats. The largest loss of neurons occurred within the CA1 field and layers 5 and 6 of the frontal cortices. The mean numbers of neurons within the cortices in rats whose treatments had been delayed for 1h were similar to those of normal rats over 700 days of age. These results support the hypothesis that neuronal loss from cumulative effects of seizure-induced brain damage simulates aging.