Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/19066 |
Resumo: | Epilepsy is a chronic neurological disease that affects 65 million people worldwide. Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults, and also the one with the highest refractoriness index to pharmacological treatment. In addition to epileptic seizures, patients with TLE suffer from medical comorbidities such as depression, anxiety, and cognitive impairment. Experimental models of epileptogenesis, such as model of TLE post-SE pilocarpine-induced, have greatly increased the understanding of the processes leading to epilepsy and, thus, potential targets for antiepileptogenic therapy. Considering the crucial role of inflammation in the development of epileptogenesis, it is believed that drugs that have anti-inflammatory effects would be an interesting strategy to prevent or reduce the consequences of epileptogenic brain insult. In this sense, statins, which are drugs used to treat dyslipidemias, present pleiotropic effects, including anti-inflammatory effect, which seems to be effective in preventing neuroinflammation and neuronal death in a variety of neurological diseases, including epilepsy. However, there are few studies on the effect of treatment with statins during the epileptogenic period. Thus, considering the potential neuroprotective effect of statins in different diseases of the central nervous system, the present study aims to evaluate the effect of treatment with atorvastatin at doses of 10 and 100 mg/kg on cognitive and behavioral changes, as well as on the susceptibility to seizures induced by PTZ during the epileptogenic process in mice submitted to the SE pilocarpine-induced. Considering the importance of the preclinical studies being developed in animals of both genders, male and female mice were used. The results show that the treatment with atorvastatin exerts a subtle disease-modifying effect, raising the convulsive threshold of the animals and improving in part the cognitive deficits, which seem to be related to its anti-inflammatory effect. In addition, the protective effects were similar in both female and male mice, except for the fact that a high dose of atorvastatin was required for females. These data reinforce the importance of developing preclinical studies in animals of both sexes. However more studies are needed to evaluate the potential effect of this statin in the treatment of epilepsy. |
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2019-11-28T18:03:59Z2019-11-28T18:03:59Z2017-03-06http://repositorio.ufsm.br/handle/1/19066Epilepsy is a chronic neurological disease that affects 65 million people worldwide. Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults, and also the one with the highest refractoriness index to pharmacological treatment. In addition to epileptic seizures, patients with TLE suffer from medical comorbidities such as depression, anxiety, and cognitive impairment. Experimental models of epileptogenesis, such as model of TLE post-SE pilocarpine-induced, have greatly increased the understanding of the processes leading to epilepsy and, thus, potential targets for antiepileptogenic therapy. Considering the crucial role of inflammation in the development of epileptogenesis, it is believed that drugs that have anti-inflammatory effects would be an interesting strategy to prevent or reduce the consequences of epileptogenic brain insult. In this sense, statins, which are drugs used to treat dyslipidemias, present pleiotropic effects, including anti-inflammatory effect, which seems to be effective in preventing neuroinflammation and neuronal death in a variety of neurological diseases, including epilepsy. However, there are few studies on the effect of treatment with statins during the epileptogenic period. Thus, considering the potential neuroprotective effect of statins in different diseases of the central nervous system, the present study aims to evaluate the effect of treatment with atorvastatin at doses of 10 and 100 mg/kg on cognitive and behavioral changes, as well as on the susceptibility to seizures induced by PTZ during the epileptogenic process in mice submitted to the SE pilocarpine-induced. Considering the importance of the preclinical studies being developed in animals of both genders, male and female mice were used. The results show that the treatment with atorvastatin exerts a subtle disease-modifying effect, raising the convulsive threshold of the animals and improving in part the cognitive deficits, which seem to be related to its anti-inflammatory effect. In addition, the protective effects were similar in both female and male mice, except for the fact that a high dose of atorvastatin was required for females. These data reinforce the importance of developing preclinical studies in animals of both sexes. However more studies are needed to evaluate the potential effect of this statin in the treatment of epilepsy.Epilepsia é uma doença neurológica crônica, que afeta cerca de 65 milhões de pessoas em todo o mundo. A epilepsia do lobo temporal (TLE) é o tipo de epilepsia focal mais comum em adultos, e também a de maior índice de refratariedade ao tratamento farmacológico. Além das crises epilépticas, os pacientes com TLE sofrem com comorbidades médicas, tais como depressão, ansiedade e alterações cognitivas. Modelos experimentais de epileptogênese, tal como o modelo da TLE pós-SE (status epilepticus) induzido por pilocarpina, têm aumentado muito a compreensão dos processos que levam à epilepsia e, assim, de potenciais alvos para terapia antiepileptogênica. Considerando o papel crucial da inflamação para o desenvolvimento da epileptogênese, acredita-se que moléculas que tenham efeitos antiinflamatórios seriam uma estratégia interessante para prevenir ou reduzir as consequências de um insulto cerebral epileptogênico. Nesse sentido, as estatinas, que são fármacos utilizados no tratamento das dislipidemias, apresentam efeitos pleiotrópicos, entre eles efeito antiinflamatório, o qual parece ser eficaz na prevenção da neuroinflamação e da morte neuronal em uma variedade de doenças neurológicas, inclusive na epilepsia. No entanto, são poucos os estudos sobre o efeito do tratamento com estatinas durante o período epileptogênico. Assim, considerando o potencial efeito neuroprotetor das estatinas em diferentes doenças do sistema nervoso central, o presente estudo tem como objetivo avaliar o efeito do tratamento com atorvastatina nas doses de 10 e 100 mg/Kg, sobre as alterações cognitivas e comportamentais, bem como na susceptibilidade as crises induzidas por PTZ durante o processo epileptogênico em camundongos submetidos ao SE induzido pela pilocarpina. Considerando a importância dos estudos pré-clínicos serem desenvolvidos em animais de ambos os sexos, camundongos machos e fêmeas foram utilizados. Os resultados obtidos mostram que o tratamento com atorvastatina exerce um sutil efeito modificador da doença, pois elevou o limiar convulsivo dos animais e melhorou parcialmente os déficits cognitivos, os quais parecem estar relacionados com o seu efeito anti-inflamatório. Além disso, os efeitos observados nos animais de ambos os sexos são similares, exceto pelo fato de que nas fêmeas uma dose maior é necessária para apresentar efeito, o que reforça a importância dos estudos pré-clínicos serem desenvolvidos em animais de ambos os sexos. No entanto mais estudos são necessários para avaliar o potencial efeito dessa estatina no tratamento da epilepsia.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEpilepsia do lobo temporalEstatinasEpileptogêneseInflamaçãoTemporal lobe epilepsyStatinsEpileptogenesisInflammationCNPQ::CIENCIAS DA SAUDE::FARMACIAEfeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpinaEfect of atorvastatin on behavioral, histological and biochemistry alterations in C57BL/6 mice submmited to status epilepticus pilocarpine-inducedinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Scorza, Fulvio Alexandrehttp://lattes.cnpq.br/3665794780601169Fighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231http://lattes.cnpq.br/2050237188678533Oliveira, Clarissa Vasconcelos de400300000005600bf52f43d-c59c-4c87-bfe1-30fdc3b04cbf9f746a87-8ab1-450e-aecc-1f75430e243bc677f64b-5cc5-4b69-a688-583d9209b1b09e5c71a6-8a49-4407-8f6c-5a4b1b506cd25fb0a545-20ef-49de-b173-3342ea92e48creponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGFARMACOLOGIA_2017_OLIVEIRA_CLARISSA.pdfTES_PPGFARMACOLOGIA_2017_OLIVEIRA_CLARISSA.pdfTese de Doutoradoapplication/pdf4181036http://repositorio.ufsm.br/bitstream/1/19066/1/TES_PPGFARMACOLOGIA_2017_OLIVEIRA_CLARISSA.pdf2ae939acb518de5ff6b10a11db2cde29MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
dc.title.alternative.eng.fl_str_mv |
Efect of atorvastatin on behavioral, histological and biochemistry alterations in C57BL/6 mice submmited to status epilepticus pilocarpine-induced |
title |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
spellingShingle |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina Oliveira, Clarissa Vasconcelos de Epilepsia do lobo temporal Estatinas Epileptogênese Inflamação Temporal lobe epilepsy Statins Epileptogenesis Inflammation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
title_full |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
title_fullStr |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
title_full_unstemmed |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
title_sort |
Efeito da atorvastatina sobre as alterações comportamentais, histológicas e bioquímicas em camundongos C57BL/6 com status epilepticus induzido por pilocarpina |
author |
Oliveira, Clarissa Vasconcelos de |
author_facet |
Oliveira, Clarissa Vasconcelos de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Mauro Schneider |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7132934163734175 |
dc.contributor.referee1.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7713953979203056 |
dc.contributor.referee2.fl_str_mv |
Scorza, Fulvio Alexandre |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3665794780601169 |
dc.contributor.referee3.fl_str_mv |
Fighera, Michele Rechia |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/8583392747509231 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2050237188678533 |
dc.contributor.author.fl_str_mv |
Oliveira, Clarissa Vasconcelos de |
contributor_str_mv |
Oliveira, Mauro Schneider Rosemberg, Denis Broock Scorza, Fulvio Alexandre Fighera, Michele Rechia |
dc.subject.por.fl_str_mv |
Epilepsia do lobo temporal Estatinas Epileptogênese Inflamação |
topic |
Epilepsia do lobo temporal Estatinas Epileptogênese Inflamação Temporal lobe epilepsy Statins Epileptogenesis Inflammation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Temporal lobe epilepsy Statins Epileptogenesis Inflammation |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Epilepsy is a chronic neurological disease that affects 65 million people worldwide. Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults, and also the one with the highest refractoriness index to pharmacological treatment. In addition to epileptic seizures, patients with TLE suffer from medical comorbidities such as depression, anxiety, and cognitive impairment. Experimental models of epileptogenesis, such as model of TLE post-SE pilocarpine-induced, have greatly increased the understanding of the processes leading to epilepsy and, thus, potential targets for antiepileptogenic therapy. Considering the crucial role of inflammation in the development of epileptogenesis, it is believed that drugs that have anti-inflammatory effects would be an interesting strategy to prevent or reduce the consequences of epileptogenic brain insult. In this sense, statins, which are drugs used to treat dyslipidemias, present pleiotropic effects, including anti-inflammatory effect, which seems to be effective in preventing neuroinflammation and neuronal death in a variety of neurological diseases, including epilepsy. However, there are few studies on the effect of treatment with statins during the epileptogenic period. Thus, considering the potential neuroprotective effect of statins in different diseases of the central nervous system, the present study aims to evaluate the effect of treatment with atorvastatin at doses of 10 and 100 mg/kg on cognitive and behavioral changes, as well as on the susceptibility to seizures induced by PTZ during the epileptogenic process in mice submitted to the SE pilocarpine-induced. Considering the importance of the preclinical studies being developed in animals of both genders, male and female mice were used. The results show that the treatment with atorvastatin exerts a subtle disease-modifying effect, raising the convulsive threshold of the animals and improving in part the cognitive deficits, which seem to be related to its anti-inflammatory effect. In addition, the protective effects were similar in both female and male mice, except for the fact that a high dose of atorvastatin was required for females. These data reinforce the importance of developing preclinical studies in animals of both sexes. However more studies are needed to evaluate the potential effect of this statin in the treatment of epilepsy. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-03-06 |
dc.date.accessioned.fl_str_mv |
2019-11-28T18:03:59Z |
dc.date.available.fl_str_mv |
2019-11-28T18:03:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/19066 |
url |
http://repositorio.ufsm.br/handle/1/19066 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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