Inflammation and Oxidative Stress in Epileptic Children: From Molecular Mechanisms to Clinical Application of Ketogenic Diet Publisher Pubmed



Ildarabadi A^{1, 2} ; Mir Mohammad Ali SN^{2, 3} ; Rahmani F^{1, 2} ; Mosavari N² ; Pourbakhtyaran E^{2, 4} ; Rezaei N^{2, 5, 6, 7} Show Affiliations
Source: Reviews in the Neurosciences Published:2024

Abstract

Childhood epilepsy affects up to 1a€» % of children. It has been shown that 30a€» % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARE£, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARE£ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms. © 2024 Walter de Gruyter GmbH, Berlin/Boston 2024.