Summary:Purpose: Mitogenic effects of seizures on granule cell progenitors in the dentate gyrus were studied in two rat models of epilepsy. We investigated which stage of epileptogenesis is critical for eliciting progenitor cell division and whether seizure-induced neuronal degeneration is responsible for the enhancement of progenitor cell division.Methods: Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neurogenesis of dentate granule cells was evaluated using the bromodeoxyuridine (BrdU) labeling method, and neuronal degeneration was assessed by in situ DNA fragmentation analysis.Results: After injection of KA, the number of BrdU-positive granule cells began to increase at day 3 after the treatment, peaked at day 5 , and returned to baseline at day 10. By day 13, the values were lower than control. After kindling, the number of BrdU-positive cells began to increase after five consecutive experiences of stage I seizures. The increase occurred from day 1 to day 3 after the last electrical stimulation, but returned to baseline by day 7. After generalized seizures were well established, repeated stimulation did not facilitate division of granule cell progenitors. DNA fragmentation was noted in pyramidal neurons in the CA1, CA3, and hilus regions at 18 h after KA injection, but not in the kindling model.Conclusions: These observations indicate that a mechanism in epileptogenesis boosts dentate progenitor cell division, but progenitor cells may become unreactive to prolonged generalized seizures. Pyramidal neuronal degeneration is not necessary for triggering the upregulation. It is suggested thal newly born granule cells may play a role in the network reorganization that occurs during epileptogenesis. Key Words: Kainic acidKindling-Neurogenesis-Bromodeoxyuridine-DNA fragmentation.Accumulating evidence reveals that generalized seizures can produce both degenerative and regenerative structural changes in the hippocampus. They include neuronal degeneration, mossy fiber synaptic reorganization, and increased neurogenesis of dentate granule cells. Hippocampal sclerosis is the most commonly encountered lesion in temporal lobe epilepsy, which is associated with a marked loss of hippocampal neurons (1).Recent immunocytochemical studies suggest that the reorganization of dentate granule cell axons, the mossy fibers, occurs in human epileptic hippocampus (2,3) and in animal models of epilepsy (4,5). Mossy fiber collat-

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