N-Formyl-Methionyl-Leucyl-Phenylalanine Plays a Neuroprotective and Anticonvulsant Role in Status Epilepticus Model.

Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory process. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/µL, 1 µL) followed by fMLP (1 mg/mL, 1 µL) or vehicle (VEH, saline 0.9%, 1 µL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine's Scale. After 24 h 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. However, our results showed that the intrahippocampal infusion of fMLP reduced 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. Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).

Role of Modulation of Hippocampal Glucose Following Pilocarpine-Induced Status Epilepticus.

Status epilepticus (SE) is defined as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, mitochondrial dysfunction, oxidative stress, and energy failure. During SE, the neurons become overexcited, increasing energy consumption. Glucose uptake is increased via the sodium glucose cotransporter 1 (SGLT1) in the hippocampus under epileptic conditions. In addition, modulation of glucose can prevent neuronal damage caused by SE. Here, we evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity, and SGLT1 expression. Vehicle (VEH, saline 0.9%, 1 µL) or glucose (GLU; 1, 2 or 3 mM, 1 µL) were administered into hippocampus of male Wistar rats (Rattus norvegicus) before or after pilocarpine to induce SE. Behavioral analysis of seizures was performed for 90 min during SE. The memory and learning processes were analyzed by the inhibitory avoidance test. After 24 h of SE, neurodegeneration process, neuronal activity, and SGLT1 expression were evaluated in hippocampal and extrahippocampal regions. Modulation of hippocampal glucose did not protect memory dysfunction followed by SE. Our results showed that the administration of glucose after pilocarpine reduced the severity of seizures, as well as the number of limbic seizures. Similarly, glucose after SE reduced cell death and neuronal activity in hippocampus, subiculum, thalamus, amygdala, and cortical areas. Finally, glucose infusion elevated the SGLT1 expression in hippocampus. Taken together our data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes via an important support of SGLT1.