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

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Role of Modulation of Hippocampal Glucose Following Pilocarpine-Induced Status Epilepticus Igor Santana de Melo 1 & Yngrid Mickaelli Oliveira dos Santos 1 & Amanda Larissa Dias Pacheco 1 & Maisa Araújo Costa 1 & Vanessa de Oliveira Silva 1 & Jucilene Freitas-Santos 1 & Cibelle de Melo Bastos Cavalcante 1 & Reginaldo Correia Silva-Filho 2 & Ana Catarina Rezende Leite 2 & Daniel Góes Leite Gitaí 1 & Marcelo Duzzioni 1 & Robinson Sabino-Silva 1,3 & Alexandre Urban Borbely 1 & Olagide Wagner de Castro 1 Received: 9 August 2020 / Accepted: 14 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

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, 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. Keywords Sodium glucose cotransporter . Epileptogenic . Glucose . Hippocampus

Introduction Status epilepticus (SE) is defined as continuous and selfsustaining seizures lasting > 30 min, reaching a significant number of patients [1–4]. Because it is an epileptogenic insult, Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s12035-02002173-0. * Olagide Wagner de Castro [email protected] 1

Department of Physiology, Institute of Biological Sciences and Health, Federal University of Alagoas (UFAL), Maceió, AL, Brazil

2

Bioenergetics Laboratory, Institute of Chemistry and Biotechnology, Federal Univers