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Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no...

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Autores principales: Zubareva, Olga E., Sinyak, Denis S., Kalita, Alisa D., Griflyuk, Alexandra V., Diespirov, Georgy P., Postnikova, Tatiana Y., Zaitsev, Aleksey V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607594/
https://www.ncbi.nlm.nih.gov/pubmed/37895080
http://dx.doi.org/10.3390/ijms242015400
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author Zubareva, Olga E.
Sinyak, Denis S.
Kalita, Alisa D.
Griflyuk, Alexandra V.
Diespirov, Georgy P.
Postnikova, Tatiana Y.
Zaitsev, Aleksey V.
author_facet Zubareva, Olga E.
Sinyak, Denis S.
Kalita, Alisa D.
Griflyuk, Alexandra V.
Diespirov, Georgy P.
Postnikova, Tatiana Y.
Zaitsev, Aleksey V.
author_sort Zubareva, Olga E.
collection PubMed
description Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy.
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spelling pubmed-106075942023-10-28 Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats Zubareva, Olga E. Sinyak, Denis S. Kalita, Alisa D. Griflyuk, Alexandra V. Diespirov, Georgy P. Postnikova, Tatiana Y. Zaitsev, Aleksey V. Int J Mol Sci Article Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy. MDPI 2023-10-20 /pmc/articles/PMC10607594/ /pubmed/37895080 http://dx.doi.org/10.3390/ijms242015400 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zubareva, Olga E.
Sinyak, Denis S.
Kalita, Alisa D.
Griflyuk, Alexandra V.
Diespirov, Georgy P.
Postnikova, Tatiana Y.
Zaitsev, Aleksey V.
Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title_full Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title_fullStr Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title_full_unstemmed Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title_short Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
title_sort antiepileptogenic effects of anakinra, lamotrigine and their combination in a lithium–pilocarpine model of temporal lobe epilepsy in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607594/
https://www.ncbi.nlm.nih.gov/pubmed/37895080
http://dx.doi.org/10.3390/ijms242015400
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