Bioenergetic Mechanisms of Seizure Control.

Richard Kovács,Zoltan Gerevich,Jakub Otáhal,Nikolaus Berndt,Alon Friedman,Ofer Prager,Siegrun Gabriel

doi:10.3389/fncel.2018.00335

Abstract

Epilepsy is characterized by the regular occurrence of seizures, which follow a stereotypical sequence of alterations in the electroencephalogram. Seizures are typically a self limiting phenomenon, concluding finally in the cessation of hypersynchronous activity and followed by a state of decreased neuronal excitability which might underlie the cognitive and psychological symptoms the patients experience in the wake of seizures. Many efforts have been devoted to understand how seizures spontaneously stop in hope to exploit this knowledge in anticonvulsant or neuroprotective therapies. Besides the alterations in ion-channels, transmitters and neuromodulators, the successive build up of disturbances in energy metabolism have been suggested as a mechanism for seizure termination. Energy metabolism and substrate supply of the brain are tightly regulated by different mechanisms called neurometabolic and neurovascular coupling. Here we summarize the current knowledge whether these mechanisms are sufficient to cover the energy demand of hypersynchronous activity and whether a mismatch between energy need and supply could contribute to seizure control.

Highlights

Bioenergetic Mechanisms of Seizure ControlRichard Kovács1*, Zoltan Gerevich, Alon Friedman, Jakub Otáhal, Ofer Prager, Siegrun Gabriel and Nikolaus Berndt
Epilepsy is a common neurological disease characterized by the manifestation of unprovoked seizures (Fisher et al, 2014)
We have recently shown that intrinsic lactate supports synaptic signaling in rat hippocampal slices and it contributes to energy demand of the restoration of transmembrane ion gradients (Angamo et al, 2016)

Summary

Bioenergetic Mechanisms of Seizure Control

Richard Kovács1*, Zoltan Gerevich, Alon Friedman, Jakub Otáhal, Ofer Prager, Siegrun Gabriel and Nikolaus Berndt. Epilepsy is characterized by the regular occurrence of seizures, which follow a stereotypical sequence of alterations in the electroencephalogram. Seizures are typically a self limiting phenomenon, concluding in the cessation of hypersynchronous activity and followed by a state of decreased neuronal excitability which might underlie the cognitive and psychological symptoms the patients experience in the wake of seizures. Besides the alterations in ion-channels, transmitters and neuromodulators, the successive build up of disturbances in energy metabolism have been suggested as a mechanism for seizure termination. Energy metabolism and substrate supply of the brain are tightly regulated by different mechanisms called neurometabolic and neurovascular coupling. We summarize the current knowledge whether these mechanisms are sufficient to cover the energy demand of hypersynchronous activity and whether a mismatch between energy need and supply could contribute to seizure control

INTRODUCTION

NEUROMETABOLIC COUPLING DURING ACUTE SEIZURES AND IN CHRONIC EPILEPTIC TISSUE

SEIZURE ASSOCIATED ALTERATIONS IN ENERGY METABOLISM INTERMEDIATES AND pH

Findings

CONCLUDING REMARKS