Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy

Abstract

Epilepsy is a common neurological disease that is not always controlled, and the ketogenic diet shows good antiepileptic effects drug-resistant epilepsy or seizures caused by specific metabolic defects via regulating the metabolism. The brain is a vital organ with high metabolic demands, and epileptic foci tend to exhibit high metabolic characteristics. Accordingly, there has been growing interest in the relationship between brain metabolism and epilepsy in recent years. To date, several new antiepileptic therapies targeting metabolic pathways have been proposed (i.e., inhibiting glycolysis, targeting lactate dehydrogenase, and dietary therapy). Promising strategies to treat epilepsy via modulating the brain's metabolism could be expected, while a lack of thorough understanding of the role of brain metabolism in the control of epilepsy remains. Herein, this review aims to provide insight into the state of the art concerning the brain's metabolic patterns and their association with epilepsy. Regulation of neuronal excitation via metabolic pathways and antiepileptic therapies targeting metabolic pathways are emphasized, which could provide a better understanding of the role of metabolism in epilepsy and could reveal potential therapeutic targets.

Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

“…Additionally, ATP deficit suppresses the effect of intermediate inhibitory neurons in the hippocampus, facilitating the spread of excitation in the neuronal network [ 6 , 12 , 13 ]. Lack of ATP molecules also results in the reduced potential of GABA-ergic inhibitory neurons, which leads to an impaired balance between excitatory and inhibitory neurons and excessive cell excitation [ 13 , 14 ].…”

“…Additionally, ATP deficit suppresses the effect of intermediate inhibitory neurons in the hippocampus, facilitating the spread of excitation in the neuronal network [ 6 , 12 , 13 ]. Lack of ATP molecules also results in the reduced potential of GABA-ergic inhibitory neurons, which leads to an impaired balance between excitatory and inhibitory neurons and excessive cell excitation [ 13 , 14 ]. Moreover, ATP deficit leads to increased glutamate release (excitatory neurotransmitter) from astrocytes to synaptic space and disturbance of the glutamate–aspartate transporter [ 1 , 13 , 15 ].…”

“…Lack of ATP molecules also results in the reduced potential of GABA-ergic inhibitory neurons, which leads to an impaired balance between excitatory and inhibitory neurons and excessive cell excitation [ 13 , 14 ]. Moreover, ATP deficit leads to increased glutamate release (excitatory neurotransmitter) from astrocytes to synaptic space and disturbance of the glutamate–aspartate transporter [ 1 , 13 , 15 ]. Other hypotheses explain seizures in MD by abnormal haemostasis of calcium ions, abnormal function of ion channels in the neural membrane, or neurotransmitter disorders [ 15 ].…”

“…Additionally, decanoic acid present in KD is a strong direct receptor inhibitor for glutamine—α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA)—which directly translates into reduced neuronal excitation. An additional benefit, especially for MD patients, is that ketone bodies are a source of energy [ 13 ]. Although the mechanism of action of KD in MD patients is not fully explained, it is known to improve the cell energy profile, lead to the stimulation of mitochondrial biogenesis in skeletal muscles, prevent the formation of abnormal mitochondria, increase ATP production in the respiratory chain, and reduce the number of COX-negative fibres (a marker of mitochondrial damage) in skeletal muscle biopsy [ 65 , 66 , 67 ].…”

Organic Bioelectronic Devices for Selective Biomarker Sensing : Towards Integration with Living Systems

“…13b). Glucose detection can also help to anticipate epileptic seizures, due to sudden glucose concentration decrease for dysregulated metabolism in some parts of the brain 151 . Glucose is the main energy source not only of the animal kingdom but also in the plant world 152 .…”