Abstracts

Rationale: Convulsive status epilepticus (SE) in adult animals leads to increased neurogenesis shortly after the insult. In later intervals, severe decline of neurogenesis was documented. Previous studies also demonstrated significant increase of neurogenesis one week after SE elicited in two-week-old rats. Nothing is however known about changes in neurogenesis in long interval after early SE. Therefore present experiment was focused on long-term changes in production of new neurons in the hippocampus of rats experiencing SE at postnatal day (P) 12. Methods: SE was induced by pilocarpine (40 mg/kg) in LiCl (3meq/kg) pretreated P12 rats. To prevent mortality and to improve recovery rats were given a single dose of paraldehyde (0.07 mg/kg) 1.5h after SE onset. Controls received saline instead pilocarpine. Animals were video/EEG monitored 5-6 mo after SE to detect spontaneous seizures. After the end of monitoring, animals were perfused and newborn neurons were detected using doublecortin (DCX) immunohistochemistry. Number of positive neurons in the dorsal hippocampus was assessed using stereological cell count in 5 consecutive sections. Adjacent sections were Nissl stained and hippocampal volume was morphometrically assessed. Results: SE developed in all 19 animals. Clinically, status epilepticus was characterized by twitching of facial muscles, chewing, head bobbing, forelimb clonus, tail erection and "swimming" movements. Paraldehyde suppressed motor seizures. Mortality after SE was 36%. Slight decrease of the body weight was seen 24h after SE (3% decrease whereas controls gained 17 % of their weight at P12). Electrographic (subclinical) seizures were detected in subpopulatin of animals. The hippocampal volume in animals with SE at P12 reached about 93% of control value, but difference was not statistically significant. When compared to controls, number of DCX-positive neurons was about 37% lower in animals with SE. Conclusions: Early SE leads to impaired dentate neurogenesis in adult rats. Whether these changes are related to epilepsy or development of comorbidities has to be further analyzed. This study was supported by grants No P302/10/0971 and No P304/12/G069 of the Grant Agency of the Czech Republic, and No ME08045 of the Ministry of Education of the Czech Republic.