Investigação do efeito do dipeptídeo Ciclo-Glicina-Prolina (CGP) no status epilépticus induzido por pilocarpina

Abstract

Epilepsy is defined as a neurological disorder characterized by hyperexcitability and hypersynchrony of neuronal populations and the presence of spontaneous recurrent seizures. About 1-2% of population are affected by this disorder and 30% of these are resistant to drug treatment. Therefore, investigations of new therapeutic tools to reduce the side effects of drugs used traditionally become of great importance. Drugs with anti-inflammatoy effect are among the promising new therapeutic tools. Cyclo-glycine-proline (CGP) has been recently characterized as anti-inflammatory effect. The objective of this study was to investigate the anticonvulsant effect of CGP in epilepsy model induced by pilocarpine. Male Wistar rats were utilized to establish three experimental groups pre-treated with CGP 10, 100 and 300 μmol/kg (ip) (n = 12), 30 minutes before Status Epilepticus (SE) induced by pilocarpine (ih) (n = 14). Animals were video monitored during SE for analyzes of behavior and euthanized 24 h after SE to analyze the neurodegeneration in the hippocampal subregions (Ammon’s horn: CA1 and CA3, and hilus) by Fluoro-Jade technique and the differential expression of GFAP and TNF-α performed by RT-qPCR. Statistical analyzes were performed using t-test (GraphPad, Prism 5.0). Regarding the behavior, we found that CGP had significant effect at a dose of 300μmol/kg compared to PILO group only in two of the analyzed parameters: latency to onset of SE and number of doses to reverse the SE. In relation to neurodegeneration, we observed a significant decrease of FJ-positive cells in animals treated with the dose of CGP 100μmol/kg in the CA1 and hilus sub-regions. Using RTQ-PCR, we observed that GFAP did not present any difference in expression of transcript levels when compared the groups treated with CGP and PILO group. TNF-α transcripts levels was lower in the group CGP with dose of 300μmol/kg compared to PILO group. Based on the findings of this study, it may be suggested that the CGP presents anticonvulsant effect in acute epileptogenesis, neuroprotective effect and in the relative expression of TNF-α.