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Abstract <p>WAG/Rij rats are a genetic model of absence epilepsy, in whichgeneralized spike-wave discharges (SWDs) are registered on EEG.SWDs are generated in the hyperexcitable somatosensory cortex ofthe brain. The antiabsence drug ethosuximide (ETX) reduces the excitabilityof the cortex and, as a result, suppresses SWDs. The work aims tofind out the recovery features of discharges after their complete suppressionby ETX. To do this, we compared the dynamics of SWD recovery aftercancellation of 14-day ETX administration to 7–8-month-old WAG/Rijrats and the age-dependent maturation of SWDs. Earlier, we showedthat the age-dependent maturation of discharges goes through 3 stages:1—immature discharges resembling spindle-like oscillations, 2—immaturedischarges in which fragments of oscillating activity alternatewith fragments of spike-wave complexes, and 3—mature SWDs. Duringage-dependent maturation of SWDs, mature discharges gradually replaceimmature ones and, at the same time, spike-wave complexes replaceoscillations. After the cancellation of ETX, only immature dischargeswere present on EEG, among which oscillations prevailed, which correspondsto the 1st stage of age-dependent development of discharges. Onthe 3rd day after drug cancellation, on EEG immature dischargesprevailed, in which oscillations alternate with spike-wave complexes,which corresponds to the 2nd stage of age-dependent developmentof discharges. On day 7, mature SWDs prevailed, which correspondsto the 3rd stage. Thus, the 3 stages of discharge recovery afterETX cancellation are similar to the stages of age-dependent evolutionof SWDs. In the process of discharge restoration, oscillations firstappeared, and then waves. Mature discharges replaced immature ones,and spike-wave complexes replaced oscillations. We assume that therestoration of discharges is the result of increased excitabilityof the somatosensory cortex of the brain after ETX cancellation.Different points of view are discussed regarding the commonalityof mechanisms or the independence of the origin of the wave andspike as indispensable attributes of a mature SWD. The results canbe used to determine the early stages of spike-wave discharges developmentfor the diagnostics and treatment of patients with absence epilepsy.</p>

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Restoration of Spike-Wave Discharges after Their Suppression with Ethosuximide in WAG/Rij Rats with Genetic Absence Epilepsy

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • A. V. Gabova,
  • E. A. Fedosova,
  • A. B. Shatskova,
  • K. Yu. Sarkisova

摘要

Abstract

WAG/Rij rats are a genetic model of absence epilepsy, in whichgeneralized spike-wave discharges (SWDs) are registered on EEG.SWDs are generated in the hyperexcitable somatosensory cortex ofthe brain. The antiabsence drug ethosuximide (ETX) reduces the excitabilityof the cortex and, as a result, suppresses SWDs. The work aims tofind out the recovery features of discharges after their complete suppressionby ETX. To do this, we compared the dynamics of SWD recovery aftercancellation of 14-day ETX administration to 7–8-month-old WAG/Rijrats and the age-dependent maturation of SWDs. Earlier, we showedthat the age-dependent maturation of discharges goes through 3 stages:1—immature discharges resembling spindle-like oscillations, 2—immaturedischarges in which fragments of oscillating activity alternatewith fragments of spike-wave complexes, and 3—mature SWDs. Duringage-dependent maturation of SWDs, mature discharges gradually replaceimmature ones and, at the same time, spike-wave complexes replaceoscillations. After the cancellation of ETX, only immature dischargeswere present on EEG, among which oscillations prevailed, which correspondsto the 1st stage of age-dependent development of discharges. Onthe 3rd day after drug cancellation, on EEG immature dischargesprevailed, in which oscillations alternate with spike-wave complexes,which corresponds to the 2nd stage of age-dependent developmentof discharges. On day 7, mature SWDs prevailed, which correspondsto the 3rd stage. Thus, the 3 stages of discharge recovery afterETX cancellation are similar to the stages of age-dependent evolutionof SWDs. In the process of discharge restoration, oscillations firstappeared, and then waves. Mature discharges replaced immature ones,and spike-wave complexes replaced oscillations. We assume that therestoration of discharges is the result of increased excitabilityof the somatosensory cortex of the brain after ETX cancellation.Different points of view are discussed regarding the commonalityof mechanisms or the independence of the origin of the wave andspike as indispensable attributes of a mature SWD. The results canbe used to determine the early stages of spike-wave discharges developmentfor the diagnostics and treatment of patients with absence epilepsy.