Ketogenic diet enriched with omega-3 fatty acids in Epilepsy: an approach focused on brain morphofunctional characteristics, cognition, clinical response, and adverse effects associated with neurodegeneration and neuroinflammation

• Grant number: 19/07056-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2019
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Kette Dualibi Ramos Valente
• Grantee: Giovanna Fernandes Ricciarelli
• Host Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The prevalence of Epilepsy is 0.5 to 1% in developed countries. It is estimated that 20 to 30% of pediatric patients are refractory to pharmacological treatment. The ketogenic diet (CD) is an adjuvant treatment to the pharmacological treatment prescribed for children and adolescents with drug-resistant Epilepsy. The composition of DC is based on a high fat content, moderate protein content and low carbohydrate content, consisting mainly of foods rich in saturated and monounsaturated fatty acids. In the literature, evidence suggests that the high consumption of n-3 PUFAS could optimize the anticonvulsant effects of CD, promoting an improvement in the inflammatory profile and, at the brain level, promoting morphofunctional alterations compatible with a better control of epileptic seizures. The present study will aim to evaluate the incorporation of omega 3 fatty acids and their impact on the morphofunctional characteristics of the brain, on cognition and on the inflammatory profile in the context of drug-resistant Epilepsy under treatment with CD. This is a study based on an experimental model with a 4-month follow-up. The number and severity of epileptic seizures will be assessed (Racine scale). Cognition will be assessed using the Morris Water Maze working memory task. From the plasma, the concentrations of ketone bodies (²hydroxybutyrate) and pro- and anti-inflammatory markers [pro-inflammatory cytokines Interleukin 1² (IL1-²), Interleukin 6 (IL6) and Tumor Necrosis Factor (TNF-á) will be evaluated and anti-inflammatory Interleukin 10 (IL10)]. In the brain will be performed analyzes of fatty acid profile and detection of cytochrome C, 3-activated caspase, NeuN, GFAP, IBA-1, and GABA-A and monocarboxylic acid transporters (MCT) type 1 and 2 (Western Blotting and immunohistochemistry). Neurodegeneration will be evaluated by histochemistry (Fluoro-Jade B). To assess brain functionality, neuroimaging analysis (microPET-CT) of 18F-FDG and 18F-flumazenil will be performed. All statistical tests will be analyzed using the Statistical Package for the Social Sciences® (SPSS) version 20.0. (AU)