Abstracts

Rationale: It is possible that levetiracetam inhibits the seizure-induced changes in neuronal plasticity that facilitates the subsequent seizure occurrence, because of its ability to depress kindling development without affecting seizures in the first trial of kindling. The recent work (Jung et al.: 2004) showed that the suppression of seizure-induced neurogenesis in the dentate gyrus attenuated spontaneous recurrent seizures following pilocarpine-induced status epilepticus, that suggested a critical role of seizure-induced neurogenesis in acquisition of epileptogenesis. To elucidate effects of levetiracetam on the seizure-induced changes in neuronal plasticity, we investigate the effects of levetiracetam on seizure-induced neurogenesis (an anomalous neuronal plasticity following seizures).Methods: Status epilepticus (SE) was induced by intracerebroventricular administration of kainic acid (KA) in adult male SD rats, which were then randomized to the post-SE treatment groups with administration of levetiracetam (KA-SE/LEV) or saline (KA-SE/saline) for 14 days intracerebroventricularly (294.2μg/day) or subcutaneously(100mg/kg/day). Rats in the control group were administered saline instead of KA and were treated with saline for 14days (non-SE/saline). Rats were injected bromodeoxyuridine (BrdU) intraperitoneally once a day on day 13 - 14, or on day 52 - 53 after KA-induced seizures and sacrificed 5 days after last BrdU injection. We counted the number of BrdU positive cells in the dentate sub-granular zone to examine changes in cell proliferation. Results: On day-14 after KA-induced seizures, the KA-SE/saline group showed a significant increase in the BrdU positive cell count compared with the non-SE/saline group. On the other hand, the BrdU positive cell count in the KA-SE/LEV group was not significantly different from that in the non-SE/saline group. The result indicated that levetiracetam significantly suppressed the increase of the dentate cell proliferation after SE. On day-53, the KA-SE/saline group showed a marked decrease in BrdU positive cell count compared with the non-SE/saline group, while the decrease of cell proliferation was not observed in the KA-SE/LEV group. Conclusions: Levetiracetam suppressed the seizure-induced changes in the dentate neurogenesis in rats, suggesting that it could prevent the development of epileptogenesis.