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Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine

Epilepsy is characterized by a predisposition to generate recurrent and spontaneous seizures; it affects millions of people worldwide. Status epilepticus (SE) is a severe type of seizure. In this context, screening potential treatments is very important. In the present study, we evaluated the benefi...

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Autores principales: Neuberger, Bruna, Mello, Fernanda Kulinski, Mallmann, Michele Pereira, da Costa Sobral, Karine Gabriela, Fighera, Michele Rechia, Royes, Luiz Fernando Freire, Furian, Ana Flávia, Sampaio, Tuane Bazanella, Oliveira, Mauro Schneider
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954593/
https://www.ncbi.nlm.nih.gov/pubmed/36831832
http://dx.doi.org/10.3390/brainsci13020289
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author Neuberger, Bruna
Mello, Fernanda Kulinski
Mallmann, Michele Pereira
da Costa Sobral, Karine Gabriela
Fighera, Michele Rechia
Royes, Luiz Fernando Freire
Furian, Ana Flávia
Sampaio, Tuane Bazanella
Oliveira, Mauro Schneider
author_facet Neuberger, Bruna
Mello, Fernanda Kulinski
Mallmann, Michele Pereira
da Costa Sobral, Karine Gabriela
Fighera, Michele Rechia
Royes, Luiz Fernando Freire
Furian, Ana Flávia
Sampaio, Tuane Bazanella
Oliveira, Mauro Schneider
author_sort Neuberger, Bruna
collection PubMed
description Epilepsy is characterized by a predisposition to generate recurrent and spontaneous seizures; it affects millions of people worldwide. Status epilepticus (SE) is a severe type of seizure. In this context, screening potential treatments is very important. In the present study, we evaluated the beneficial effects of rosmarinic acid (RA) in pilocarpine-induced in vitro and in vivo models of epileptiform activity. Using an in vitro model in combined entorhinal cortex–hippocampal from Wistar rats we evaluated the effects of RA (10 µg/mL) on the lactate release and a glucose fluorescent analogue, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NDBG), after incubation in high potassium aCSF supplemented or not with pilocarpine. In the in vivo model, SE was induced in male C57BL/6 mice by pilocarpine. At 1, 24, and 48 h after the end of SE mice were treated with RA (30 mg/kg/v.o.). We evaluated the neuromotor impairment by neuroscore tests and protein carbonyl levels in the cerebral cortex. In both in vitro models, RA was able to decrease the stimulated lactate release, while no effect on 2-NBDG uptake was found. RA has beneficial effects in models of epileptiform activity in vivo and in vitro. We found that RA treatment attenuated SE-induced neuromotor impairment at the 48 h timepoint. Moreover, post-SE treatment with RA decreased levels of protein carbonyls in the cerebral cortex of mice when compared to their vehicle-treated counterparts. Importantly, RA was effective in a model of SE which is relevant for the human condition. The present data add to the literature on the biological effects of RA, which could be a good candidate for add-on therapy in epilepsy.
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spelling pubmed-99545932023-02-25 Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine Neuberger, Bruna Mello, Fernanda Kulinski Mallmann, Michele Pereira da Costa Sobral, Karine Gabriela Fighera, Michele Rechia Royes, Luiz Fernando Freire Furian, Ana Flávia Sampaio, Tuane Bazanella Oliveira, Mauro Schneider Brain Sci Article Epilepsy is characterized by a predisposition to generate recurrent and spontaneous seizures; it affects millions of people worldwide. Status epilepticus (SE) is a severe type of seizure. In this context, screening potential treatments is very important. In the present study, we evaluated the beneficial effects of rosmarinic acid (RA) in pilocarpine-induced in vitro and in vivo models of epileptiform activity. Using an in vitro model in combined entorhinal cortex–hippocampal from Wistar rats we evaluated the effects of RA (10 µg/mL) on the lactate release and a glucose fluorescent analogue, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NDBG), after incubation in high potassium aCSF supplemented or not with pilocarpine. In the in vivo model, SE was induced in male C57BL/6 mice by pilocarpine. At 1, 24, and 48 h after the end of SE mice were treated with RA (30 mg/kg/v.o.). We evaluated the neuromotor impairment by neuroscore tests and protein carbonyl levels in the cerebral cortex. In both in vitro models, RA was able to decrease the stimulated lactate release, while no effect on 2-NBDG uptake was found. RA has beneficial effects in models of epileptiform activity in vivo and in vitro. We found that RA treatment attenuated SE-induced neuromotor impairment at the 48 h timepoint. Moreover, post-SE treatment with RA decreased levels of protein carbonyls in the cerebral cortex of mice when compared to their vehicle-treated counterparts. Importantly, RA was effective in a model of SE which is relevant for the human condition. The present data add to the literature on the biological effects of RA, which could be a good candidate for add-on therapy in epilepsy. MDPI 2023-02-08 /pmc/articles/PMC9954593/ /pubmed/36831832 http://dx.doi.org/10.3390/brainsci13020289 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
Neuberger, Bruna
Mello, Fernanda Kulinski
Mallmann, Michele Pereira
da Costa Sobral, Karine Gabriela
Fighera, Michele Rechia
Royes, Luiz Fernando Freire
Furian, Ana Flávia
Sampaio, Tuane Bazanella
Oliveira, Mauro Schneider
Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title_full Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title_fullStr Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title_full_unstemmed Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title_short Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine
title_sort beneficial effects of rosmarinic acid in vitro and in vivo models of epileptiform activity induced by pilocarpine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954593/
https://www.ncbi.nlm.nih.gov/pubmed/36831832
http://dx.doi.org/10.3390/brainsci13020289
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