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BIBTEX RIS

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

2016; Elsevier BV; Volume: 61; Linguagem: Inglês

10.1016/j.yebeh.2016.05.026

1525-5069

Igor Santana de Melo, Yngrid Mickaelli Oliveira dos Santos, Maisa Araújo Costa, Amanda Larissa Dias Pacheco, Nívea K.G.T. Silva, Léia Cardoso-Sousa, Ulises Pereira, Luíz Ricardo Goulart, Norberto Garcia‐Cairasco, Marcelo Duzzioni, Daniel Leite Góes Gitaí, Cristiane Queixa Tilelli, Robinson Sabino‐Silva, Olagide Wagner de Castro,

Drug Transport and Resistance Mechanisms

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 μL) or phlorizin, a specific SGLT inhibitor (PZN, 1 μL, 50 μg/μL), 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.