N-formil-metionil-leucil-fenilalanina desempenha um papel neuroprotetor e anticonvulsivante no modelo de status epilepticus

Abstract

Status epilepticus (SE) is described as continuous and self-sustaining seizures, which leads to hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory mechanisms. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptide in behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2mg/μL, 1μL) followed by FMLP (1mg/mL, 1μL) or vehicle (VEH, saline 0.9%, 1μL). During the 90 minutes of SE, epileptic seizures were analyzed according to the Racine’s Scale. After 24 hours of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. Our results showed that the infusion of fMLP was able to reduce the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy.