Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus

The administration of lithium–pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When tre...

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Main Authors: José Eduardo Marques-Carneiro, Astrid Nehlig, Jean-Christophe Cassel, Eduardo Ferreira Castro-Neto, Julia Julie Litzahn, Anne Pereira de Vasconcelos, Maria da Graça Naffah-Mazacoratti, Maria José da Silva Fernandes
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/10/4/85
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author José Eduardo Marques-Carneiro
Astrid Nehlig
Jean-Christophe Cassel
Eduardo Ferreira Castro-Neto
Julia Julie Litzahn
Anne Pereira de Vasconcelos
Maria da Graça Naffah-Mazacoratti
Maria José da Silva Fernandes
author_facet José Eduardo Marques-Carneiro
Astrid Nehlig
Jean-Christophe Cassel
Eduardo Ferreira Castro-Neto
Julia Julie Litzahn
Anne Pereira de Vasconcelos
Maria da Graça Naffah-Mazacoratti
Maria José da Silva Fernandes
author_sort José Eduardo Marques-Carneiro
collection DOAJ
description The administration of lithium–pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS. Thus, we performed high-performance liquid chromatography (HPLC) to quantify levels of amino acids and monoamines, and c-Fos immunohistochemical labeling to map cerebral activation during seizures. Comparing rats treated one hour after SE onset with saline (CT), CRS, or diazepam (DZP), HPLC showed that 4 h after SE onset, dopamine (DA), norepinephrine (NE), and GABA levels were normal, whereas serotonin levels were increased. Using c-Fos labeling, we demonstrated increased activity in thalamic mediodorsal (MD) and laterodorsal (LD) nuclei in rats treated with CRS. In summary, at early times, CRS seems to modulate excitability by acting on some monoamine levels and increasing activity of MD and LD thalamic nuclei, suggesting a possible involvement of these nuclei in insult- and/or epileptogenesis-modifying effects of CRS.
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spelling doaj.art-82658a734dd743fc9ec6d40fb32d2c0c2022-12-22T01:16:47ZengMDPI AGPharmaceuticals1424-82472017-11-011048510.3390/ph10040085ph10040085Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status EpilepticusJosé Eduardo Marques-Carneiro0Astrid Nehlig1Jean-Christophe Cassel2Eduardo Ferreira Castro-Neto3Julia Julie Litzahn4Anne Pereira de Vasconcelos5Maria da Graça Naffah-Mazacoratti6Maria José da Silva Fernandes7Departamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, BrazilInstitut National de la Santé et de la Recherche Médicale (INSERM-U 1129)—Infantile Epilepsies and Brain Plasticity, 75654 Paris, FranceUnistra, Laboratoire de Neurosciences Cognitives et Adaptatives—Université de Strasbourg, Faculté de Psychologie, 67000 Strasbourg, FranceDepartamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, BrazilDepartamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, BrazilUnistra, Laboratoire de Neurosciences Cognitives et Adaptatives—Université de Strasbourg, Faculté de Psychologie, 67000 Strasbourg, FranceDepartamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, BrazilDepartamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, BrazilThe administration of lithium–pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS. Thus, we performed high-performance liquid chromatography (HPLC) to quantify levels of amino acids and monoamines, and c-Fos immunohistochemical labeling to map cerebral activation during seizures. Comparing rats treated one hour after SE onset with saline (CT), CRS, or diazepam (DZP), HPLC showed that 4 h after SE onset, dopamine (DA), norepinephrine (NE), and GABA levels were normal, whereas serotonin levels were increased. Using c-Fos labeling, we demonstrated increased activity in thalamic mediodorsal (MD) and laterodorsal (LD) nuclei in rats treated with CRS. In summary, at early times, CRS seems to modulate excitability by acting on some monoamine levels and increasing activity of MD and LD thalamic nuclei, suggesting a possible involvement of these nuclei in insult- and/or epileptogenesis-modifying effects of CRS.https://www.mdpi.com/1424-8247/10/4/85carisbamate 1temporal-lobe epilepsy 2brain activity 3
spellingShingle José Eduardo Marques-Carneiro
Astrid Nehlig
Jean-Christophe Cassel
Eduardo Ferreira Castro-Neto
Julia Julie Litzahn
Anne Pereira de Vasconcelos
Maria da Graça Naffah-Mazacoratti
Maria José da Silva Fernandes
Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
Pharmaceuticals
carisbamate 1
temporal-lobe epilepsy 2
brain activity 3
title Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
title_full Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
title_fullStr Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
title_full_unstemmed Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
title_short Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus
title_sort neurochemical changes and c fos mapping in the brain after carisbamate treatment of rats subjected to lithium pilocarpine induced status epilepticus
topic carisbamate 1
temporal-lobe epilepsy 2
brain activity 3
url https://www.mdpi.com/1424-8247/10/4/85
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