Ion dynamics underlying the seizure delay effect of low-frequency electrical stimulation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985807%3A_____%2F25%3A00644273" target="_blank" >RIV/67985807:_____/25:00644273 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023752:_____/25:43921646 RIV/00216208:11130/25:10507254

Výsledek na webu

<a href="https://doi.org/10.1371/journal.pcbi.1013838" target="_blank" >https://doi.org/10.1371/journal.pcbi.1013838</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pcbi.1013838" target="_blank" >10.1371/journal.pcbi.1013838</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ion dynamics underlying the seizure delay effect of low-frequency electrical stimulation

Popis výsledku v původním jazyce

The biological mechanisms underlying the spontaneous and recurrent transition to seizures in the epileptic brain are still poorly understood. As a result, seizures remain uncontrolled in a substantial proportion of patients. Brain stimulation is an emerging and promising method to treat various brain disorders, including drug-refractory epilepsy. Selected stimulation protocols previously demonstrated therapeutic efficacy in reducing the seizure rate. The stimulation efficacy critically depends on chosen stimulation parameters, such as the time point, amplitude, and frequency of stimulation. This study aims to explore the neurobiological impact of 1Hz stimulation and provide the mechanistic explanation behind its seizure-delaying effects. We study this effect using a computational model, a modified version of the Epileptor-2 model, in close comparison with such stimulation effects on spontaneous seizures recorded in vitro in a high-potassium model of ictogenesis in rat hippocampal slices. In particular, we investigate the mechanisms and dynamics of spontaneous seizure emergence, the seizure-delaying effect of the stimulation, and the optimal stimulation parameters to achieve the maximal anti-seizure effect. We show that the modified Epileptor-2 model replicates key experimental observations, and captures seizure dynamics and the anti-seizure effects of low-frequency electrical stimulation (LFES) observed in hippocampal slices. We identify the critical thresholds in the model for seizure onset and determine the optimal stimulation parameters—timing, amplitude, and duration—that exceed specific thresholds to delay seizures without triggering premature seizures. Our study highlights the central role of sodium-potassium pump dynamics in terminating seizures and mediating the LFES effect.

Název v anglickém jazyce

Ion dynamics underlying the seizure delay effect of low-frequency electrical stimulation

Popis výsledku anglicky

The biological mechanisms underlying the spontaneous and recurrent transition to seizures in the epileptic brain are still poorly understood. As a result, seizures remain uncontrolled in a substantial proportion of patients. Brain stimulation is an emerging and promising method to treat various brain disorders, including drug-refractory epilepsy. Selected stimulation protocols previously demonstrated therapeutic efficacy in reducing the seizure rate. The stimulation efficacy critically depends on chosen stimulation parameters, such as the time point, amplitude, and frequency of stimulation. This study aims to explore the neurobiological impact of 1Hz stimulation and provide the mechanistic explanation behind its seizure-delaying effects. We study this effect using a computational model, a modified version of the Epileptor-2 model, in close comparison with such stimulation effects on spontaneous seizures recorded in vitro in a high-potassium model of ictogenesis in rat hippocampal slices. In particular, we investigate the mechanisms and dynamics of spontaneous seizure emergence, the seizure-delaying effect of the stimulation, and the optimal stimulation parameters to achieve the maximal anti-seizure effect. We show that the modified Epileptor-2 model replicates key experimental observations, and captures seizure dynamics and the anti-seizure effects of low-frequency electrical stimulation (LFES) observed in hippocampal slices. We identify the critical thresholds in the model for seizure onset and determine the optimal stimulation parameters—timing, amplitude, and duration—that exceed specific thresholds to delay seizures without triggering premature seizures. Our study highlights the central role of sodium-potassium pump dynamics in terminating seizures and mediating the LFES effect.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Computational Biology

ISSN

1553-734X

e-ISSN

1553-7358

Svazek periodika

21

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

e1013838

Kód UT WoS článku

001650641700004

EID výsledku v databázi Scopus

2-s2.0-105026587621