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

Departamento de Neurologia e Neurocirurgia, Disciplina Neurociência, Universidade Federal de São Paulo, São Paulo 04021-001, Brazil
Unistra, Laboratoire de Neurosciences Cognitives et Adaptatives—Université de Strasbourg, Faculté de Psychologie, 67000 Strasbourg, France
Centre National de la Recherche Scientifique (CNRS), UMR 7364, LNCA, 12 rue Goethe, 67000 Strasbourg, France
Institut National de la Santé et de la Recherche Médicale (INSERM-U 1129)—Infantile Epilepsies and Brain Plasticity, 75654 Paris, France
Université Paris Descartes, Sorbonne Paris Cité, 91190 Gif-sur-Yvette, France
Author to whom correspondence should be addressed.
Pharmaceuticals 2017, 10(4), 85;
Received: 15 September 2017 / Revised: 20 October 2017 / Accepted: 27 October 2017 / Published: 1 November 2017
(This article belongs to the Special Issue Epilepsy and Neurodegeneration: Current Therapeutic Implications)
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. View Full-Text
Keywords: carisbamate 1; temporal-lobe epilepsy 2; brain activity 3 carisbamate 1; temporal-lobe epilepsy 2; brain activity 3
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Marques-Carneiro, J.E.; Nehlig, A.; Cassel, J.-C.; Castro-Neto, E.F.; Litzahn, J.J.; Pereira de Vasconcelos, A.; Naffah-Mazacoratti, M.D.G.; Fernandes, M.J.S. Neurochemical Changes and c-Fos Mapping in the Brain after Carisbamate Treatment of Rats Subjected to Lithium–Pilocarpine-Induced Status Epilepticus. Pharmaceuticals 2017, 10, 85.

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