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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MDPI AG
2017-11-01
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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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