Abstracts

Rationale: Mesial temporal lobe epilepsy is characterized by severe neuronal loss in the hilus of the dentate gyrus and in the Cornu Ammonis regions 1, 3 and 4 (CA1-4). This feature can be experimentally reproduced in the model of status epilepticus (SE) induced in rodents by intrahippocampal application of pilocarpina (PILO). To date, in this experimental model, there are no available data regarding the effect of the delay to anticonvulsant therapy application on the severity of hippocampal neuronal lesion. Then, our main goal was to characterize hippocampal neuronal degeneration in rats presenting SE treated with diazepam (DZP) one, two or four hours after its onset, in the model of SE induced by intrahippocampal application of PILO.Methods: To induce SE, PILO was applied into the adult rat s right hippocampus. One (1-h; n=10), two (2-h; n=9) and four hours (4-h; n=7) after the SE-onset, the animals were treated with DZP (10mg/Kg; i.p.). Rats with application of saline solution in the hippocampus were used as control group (n=10). Seven days after the end of the SE, all rats were euthanized and their brains were collected, processed with Fluoro-Jade C staining and degenerating neurons (FJC+ cells) were quantified in hippocampal fields. Results: 1) all rats from the SE groups showed SE with limbic generalized seizures during at least 50% of the period before DZP therapy; 2) between 2 and 4,5 hours after the DZP application, 40, 56 and 71% of rats from the 1, 2 and 4h groups, respectively, displayed recurrent convulsive seizures, during at least 18 hours; 3) the control group did not present FJC+ cells; 4) the number of FJC+ cells was similar between rats from all SE groups that showed seizures after DZP application and between rats from all SE groups without or with occasional recurrent seizures after DZP application (p>0,05; ANOVA); and 5) rats with recurrent seizures after DZP therapy showed higher number of FJC+ cells in bilateral CA1, CA3a and CA4 (p 0,01; ANOVA) than rats without or with occasional recurrent seizures.Conclusions: In the model of SE induced by intrahippocampal PILO, there is not a relation between the delay to DZP application and the severity of hippocampal neuronal degeneration. The recurrence of convulsive SE after DZP application was strongly associated with hippocampal neuronal degeneration. These data indicate that the control of SE after DZP therapy is fundamental for control of the hippocampal neuronal degeneration.