Papel da modulação de glicose hipocampal após status epilepticus induzido por pilocarpina

Abstract

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, a supply of glucose can prevent neuronal damage caused by SE. We evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity and SGLT1expression. Vehicle (VEH, saline 0.9%, 1μL) or glucose (GLU; 1, 2 or 3mM) were administered into hippocampus before or after pilocarpine (PILO) to induce SE. Behavioral analysis of seizures was performed for 90 minutes during of SE, according to Racine scale. The memory and learning processes were analyzed by the inhibitory avoidance test. After 24 hours of SE, neurodegeneration process, neuronal activity and SGLT1 expression were evaluated in hippocampal and extrahipocampal regions by Fluoro-Jade C (FJ-C histochemistry, c-Fos and SGLT1 immunofluorescence, respectively. The administration of glucose after PILO reduced the severity of seizures, as well as the number of limbic seizures classes 3-5. In addition, modulation of hippocampal glucose protected memory dysfunction followed by SE. Similarly, glucose after PILO attenuated the number of FJ+ and c-Fos+ neurons in hippocampus, subiculum, thalamus and cortical areas. Finally, SGLT1 expression was elevated in hippocampus after increasing glucose levels. These data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes via an important support of SGLT1.