Impact of high polyunsaturated fatty acid ketogenic diet on epileptic seizure control and cognition: correlation with histological and functional aspects

• Grant number: 21/14144-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2022
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Kette Dualibi Ramos Valente
• Grantee: Kette Dualibi Ramos Valente
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Emerson Soares Bernardes ; Gilberto Fernando Xavier ; Maria José da Silva Fernandes

Abstract

A portion of pediatric patients are drug resistant to conventional drug treatment for epilepsy. The ketogenic diet (KD) has been proposed as an adjuvant to the pharmacological treatment prescribed for children and adolescents with drug-resistant epilepsy. Evidence suggests that the high consumption of PUFAs, especially omega 3, optimizes the anti-seizure effects of KD, promoting an improvement in the inflammatory profile, morphofunctional alterations compatible with a better control of seizures, and minimizing the cognitive damage caused by recurrent epileptic crises. The present study will evaluate the impact of PUFA-DC, with and without omega-3 complementation, on the control of epileptic seizures, on cognition and on the histological and functional characteristics of the brain, as well as on neuroinflammation. This is a preclinical study based on an experimental model of Li-Pilo-induced epilepsy, with a 4-month follow-up. After induction, the animals will be randomized into five groups: (1) standard diet epilepsy group (EPI-DP), (2) standard diet control group (CT-DP), (3) PUFAS-DC n3 control group (CT- P3), (4) PUFAS-DC epilepsy group (EPI-PDC), and (5) PUFAS-DC n3 epilepsy group (EPI-P3). The animals will be treated with control feed or PUFA-DC, with or without omega 3 supplementation, for 45 days. The number and severity of crises will be evaluated (Racine scale). Cognition will be assessed through the working memory task in the Morris Aquatic Maze. From the plasma, the concentrations of ketone bodies (²-hydroxybutyrate) and pro- and anti-inflammatory markers [pro-inflammatory cytokines Interleukin 1² (IL1-²), Interleukin 6 (IL6) and Tumor Necrosis Factor (TNF-) 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 Social Sciences® (SPSS) version 20.0. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, ANNA LECTICIA; MONTENEGRO, MARIA AUGUSTA; VALENTE, KETTE; SAMPAIO, LETICIA BRITO. Ketogenic diet therapy for epilepsy: Clinical pearls. Epilepsy & Behavior, v. 161, p. 9-pg., 2024-10-28. (19/26960-7, 21/14144-0, 19/07056-8)