Abstracts

Rationale: It is advocated the first epileptic seizure causes continuously pathological and electrophysiological change in hippocampus, leading to the development of epileptogenesis. The preventive treatment with anti-epileptic drugs has a prospect against the development of epileptogenesis. We evaluated the effect of continuous treatment with levetiracetam (LEV) on pathological changes in epileptic mice hippocampi. Methods: Eight week-old male C57BL6 mice were used in our study. We classified them into three groups: Group A was treated with saline injection for 5 days after the development of status epilepticus (SE), Group B was treated with LEV (200mg/kg/day i.p.) for 5 days after SE, and Group C was injected saline for 5days without SE. SE was induced by pilocarpine injection (280mg/kg i.p.), and all animals were treated with diazepam (10mg/kg i.p.) to sedate SE. We injected Green Fluorescence Protein (GFP)-labeled retrovirus into bilateral hippocampal dentate gyrus (DG) stereotactically two days after pilocarpine injection to visualize mitotic newborn neurons. All mice were euthanized 14 days after development of SE and then removed a brain. We compared the number of GFP-labeled newborn cells in DG among three groups and performed statistic analysis with ANOVA (p-value: <0.05). We also compared the morphological features of newborn cells among three animal groups. Results: The number of GFP-positive newborn neurons in DG was significantly lower in group B comparing to group A (P<0.01). Other GFP-positive newborn cells co-stained with NG2 was also detected and the number of them in group B was significantly lower than group A. The form of axons in group A was extremely irregular. There was no difference between group B and C, suggesting that continuous treatment with LEV inhibited epilepsy-induced neurogenesis. Conclusions: Continuous treatment with LEV suppressed epilepsy-induced neurogenesis in mice hippocampus. Preventive treatment with LEV has potentials to inhibit pathological changes in hippocampus.