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The role of thrombin in early-onset seizures

A variety of clinical observations and studies in animal models of temporal lobe epilepsy (TLE) reveal dysfunction of blood-brain barrier (BBB) during seizures. It is accompanied by shifts in ionic composition, imbalance in transmitters and metabolic products, extravasation of blood plasma proteins...

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Autores principales: Savotchenko, Alina, Klymenko, Mariia, Shypshyna, Mariia, Isaev, Dmytro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034332/
https://www.ncbi.nlm.nih.gov/pubmed/36970419
http://dx.doi.org/10.3389/fncel.2023.1101006
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author Savotchenko, Alina
Klymenko, Mariia
Shypshyna, Mariia
Isaev, Dmytro
author_facet Savotchenko, Alina
Klymenko, Mariia
Shypshyna, Mariia
Isaev, Dmytro
author_sort Savotchenko, Alina
collection PubMed
description A variety of clinical observations and studies in animal models of temporal lobe epilepsy (TLE) reveal dysfunction of blood-brain barrier (BBB) during seizures. It is accompanied by shifts in ionic composition, imbalance in transmitters and metabolic products, extravasation of blood plasma proteins in the interstitial fluid, causing further abnormal neuronal activity. A significant amount of blood components capable of causing seizures get through the BBB due to its disruption. And only thrombin has been demonstrated to generate early-onset seizures. Using the whole-cell recordings from the single hippocampal neurons we recently showed the induction of epileptiform firing activity immediately after the addition of thrombin to the blood plasma ionic media. In the present work, we mimic some effects of BBB disruption in vitro to examine the effect of modified blood plasma artificial cerebrospinal fluid (ACSF) on the excitability of hippocampal neurons and the role of serum protein thrombin in seizure susceptibility. Comparative analysis of model conditions simulating BBB dysfunction was performed using the lithium-pilocarpine model of TLE, which most clearly reflects the BBB disruption in the acute stage. Our results demonstrate the particular role of thrombin in seizure-onset in conditions of BBB disruption.
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spelling pubmed-100343322023-03-24 The role of thrombin in early-onset seizures Savotchenko, Alina Klymenko, Mariia Shypshyna, Mariia Isaev, Dmytro Front Cell Neurosci Cellular Neuroscience A variety of clinical observations and studies in animal models of temporal lobe epilepsy (TLE) reveal dysfunction of blood-brain barrier (BBB) during seizures. It is accompanied by shifts in ionic composition, imbalance in transmitters and metabolic products, extravasation of blood plasma proteins in the interstitial fluid, causing further abnormal neuronal activity. A significant amount of blood components capable of causing seizures get through the BBB due to its disruption. And only thrombin has been demonstrated to generate early-onset seizures. Using the whole-cell recordings from the single hippocampal neurons we recently showed the induction of epileptiform firing activity immediately after the addition of thrombin to the blood plasma ionic media. In the present work, we mimic some effects of BBB disruption in vitro to examine the effect of modified blood plasma artificial cerebrospinal fluid (ACSF) on the excitability of hippocampal neurons and the role of serum protein thrombin in seizure susceptibility. Comparative analysis of model conditions simulating BBB dysfunction was performed using the lithium-pilocarpine model of TLE, which most clearly reflects the BBB disruption in the acute stage. Our results demonstrate the particular role of thrombin in seizure-onset in conditions of BBB disruption. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034332/ /pubmed/36970419 http://dx.doi.org/10.3389/fncel.2023.1101006 Text en Copyright © 2023 Savotchenko, Klymenko, Shypshyna and Isaev. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Savotchenko, Alina
Klymenko, Mariia
Shypshyna, Mariia
Isaev, Dmytro
The role of thrombin in early-onset seizures
title The role of thrombin in early-onset seizures
title_full The role of thrombin in early-onset seizures
title_fullStr The role of thrombin in early-onset seizures
title_full_unstemmed The role of thrombin in early-onset seizures
title_short The role of thrombin in early-onset seizures
title_sort role of thrombin in early-onset seizures
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034332/
https://www.ncbi.nlm.nih.gov/pubmed/36970419
http://dx.doi.org/10.3389/fncel.2023.1101006
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