Análise funcional de cotransportadores de sódio/glicose (SGLT) no Status Epilepticus induzido por microinjeção hipocampal de pilocarpina

Abstract

Temporal Lobe Epilepsy (TLE) is characterized by recurrent spontaneous seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as Status Epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na+/glucose cotransporters (SGLT) on hippocampus was unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after PILO-induced SE. Vehicle (VEH, 1μL) or phlorizin, a specific SGLT inhibitor (PZN, 1μL, 50μg/μL), were administered in the hippocampus of rats 30 minutes before PILO-induced SE (VEH+PILO or PZN+PILO, respectively). The limbic seizures were classified using the Racine’s scale and the amount of Wet Dog Shake (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade (FJ) and FJ positive neurons (FJ+) were counted 24h and 15 days after SE. PZN-treated rats showed higher (p<0.05) number of WDS in relation to VEH+PILO. The seizure severity was not significant between PZN+PILO and VEH+PILO groups. However, the pattern of limbic seizures significantly changed in PZN+PILO. Indeed the class 5 seizures repeated itself more times (p<0.05) than the other classes in PZN group at 50, 60 and 70 min after SE induction. PZN+PILO animals had a higher (p<0.05) number of FJ+ in the dentate gyrus (DG), hilus, CA3 and CA1 of hippocampus when compared with VEH+PILO. Interestingly, 15 days after SE induction, PZN+PILO animals had a decreased number (p<0.05) of FJ+ in CA1 compared to VEH+PILO. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures in a specific time point (50-70 min) during SE. Besides, the inhibition of SGLT function in hippocampus also increases neurodegeneration in hippocampus 24h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stage of epileptogenic processes.