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

Mol Neurobiol. 2021 Mar;58(3):1217-1236. doi: 10.1007/s12035-020-02173-0. Epub 2020 Oct 29.

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: Epileptogenic; Glucose; Hippocampus; Sodium glucose cotransporter.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Biomarkers / metabolism
  • Cell Death
  • Glucose / metabolism*
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Memory Consolidation
  • Neurons / pathology
  • Oxidative Stress
  • Pilocarpine
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Sodium-Glucose Transporter 1 / metabolism
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / metabolism*
  • Status Epilepticus / physiopathology

Substances

  • Antioxidants
  • Biomarkers
  • Sodium-Glucose Transporter 1
  • Pilocarpine
  • Glucose