Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampusu

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Melo, Igor S. ; Santos, Yngrid M. O. ; Costa, Maisa A. ; Pacheco, Amanda L. D. ; Silva, Nivea K. G. T. ; Cardoso-Sousa, L. ; Pereira, U. P. ; Goulart, L. R. ; Garcia-Cairasco, Norberto ; Duzzioni, Marcelo ; Gitai, Daniel L. G. ; Tilelli, Cristiane Q. ; Sabino-Silva, Robinson ; Castro, Olagide W.

• Tipo de documento: Artigo Científico
• Fonte: Epilepsy & Behavior; v. 61, p. 258-268, AUG 2016.
• Citações Web of Science: 4

Resumo

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent 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 (SGLTs) on hippocampus during SE is still unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after pilocarpine (PILO)-induced SE. Vehicle (VEH, 1 mu L) or phlorizin, a specific SGLT inhibitor (PZN, 1 mu L, 50 mu g/mu L), was administered in the hippocampus of rats 30 min before PILO (VEH + PILO or PZN + PILO, respectively). The limbic seizures were classified using the Racine's scale, and the amount of wet dog shakes (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade C (FJ-C), and FJ-C-positive neurons (FJ-C+) were counted 24 h and 15 days after SE. The PZN-treated rats showed higher (p < 0.05) number of WDS when compared with VEH + PILO. There was no difference in seizure severity between PZN + PILO and VEH + PILO groups. However, the pattern of limbic seizures significantly changed in PZN + PILO. Indeed, the class 5 seizures repeated themselves more times (p < 0.05) than the other classes in the PZN group at 50 min after SE induction. The PZN + PILO animals had a higher (p < 0.05) number of FJ-C + cells in the dentate gyrus (DG), hilus, and CA3 and CA1 of hippocampus, when compared with VEH + PILO. The PZN + PILO animals had a decreased number (p < 0.05) of FJ-C+ cells in CA1 compared with VEH + PILO 15 days after SE induction. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures during SE and increased neurodegeneration in hippocampus 24 h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stages of epileptogenic processes. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 07/50261-4 - Neurociências, epilepsia e arte: caracterização interdisciplinar da cepa WAR e modelos de epilepsia correlacionados: as oficinas Da Vinci, divulgação científica e quebras de estigmas em epilepsia
• Beneficiário: Norberto Garcia Cairasco
• Modalidade de apoio: Auxílio à Pesquisa - Temático