Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial

Detalhes bibliográficos
Autor(a) principal: Goldim, Mariana Pereira de Souza
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Universitário da Ânima (RUNA)
Texto Completo: https://repositorio.animaeducacao.com.br/handle/ANIMA/2994
Resumo: Introduction: Behavioral and physiological alterations occur due inflammatory process, called as sickness behavior. Sepsis is an overwhelmed systemic inflammation response due an infection, leading to organ damage, including brain, causing neurological alterations and cognitive brain damage. Objective: Investigate sickness behavior and its involvement with neuroinflammation and cognitive damage in experimental sepsis. Methods: Male Wistar rats of two months of age were submitted to sepsis model of cecal ligation and puncture (CLP group) or laparotomy only (sham group). Sickness behavior were evaluated prior surgery, 6h, 12h and 24h after, for analysis of acute neuroinflammation and blood-brain barrier (BBB) leakage at brain structures: amygdala, nucleus accumbens, hippocampus and prefrontal cortex at 24h after CLP. Or daily evaluations during eight days for analysis of long term neuroinflammation and cognitive damage. Sickness behavior were determined by the following criteria: hypothermia, anorexia, adipsia, anhedonia and lethargy. The sickness behavior score (SBS) were determined by the alteration of healthy behavior prior sepsis. Also, were evaluated the involvement of microglia activation, by inhibition of M1 microglia by minocycline. Results: CLP animals showed increased sickness behavior in acute and chronic evaluation. It was observed an association of SBS and BBB leakage, IL-6 cytokine, corticosterone, BDNF, nitrite/nitrate levels and neuroinflammation in amygdala. Chronic SBS was associated with long term cognitive damage. Microglial activation showed to be involved with SBS, neuroinflammation and cognitive damage. Conclusion: Physiological alterations of sickness behavior are associated with inflammation markers and damage to CNS. Being this protocol of behavioral evaluation help the analysis of CNS alterations and pathways involved in sepsis.
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spelling Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglialComportamento doentioSepseNeuroinflamaçãoIntroduction: Behavioral and physiological alterations occur due inflammatory process, called as sickness behavior. Sepsis is an overwhelmed systemic inflammation response due an infection, leading to organ damage, including brain, causing neurological alterations and cognitive brain damage. Objective: Investigate sickness behavior and its involvement with neuroinflammation and cognitive damage in experimental sepsis. Methods: Male Wistar rats of two months of age were submitted to sepsis model of cecal ligation and puncture (CLP group) or laparotomy only (sham group). Sickness behavior were evaluated prior surgery, 6h, 12h and 24h after, for analysis of acute neuroinflammation and blood-brain barrier (BBB) leakage at brain structures: amygdala, nucleus accumbens, hippocampus and prefrontal cortex at 24h after CLP. Or daily evaluations during eight days for analysis of long term neuroinflammation and cognitive damage. Sickness behavior were determined by the following criteria: hypothermia, anorexia, adipsia, anhedonia and lethargy. The sickness behavior score (SBS) were determined by the alteration of healthy behavior prior sepsis. Also, were evaluated the involvement of microglia activation, by inhibition of M1 microglia by minocycline. Results: CLP animals showed increased sickness behavior in acute and chronic evaluation. It was observed an association of SBS and BBB leakage, IL-6 cytokine, corticosterone, BDNF, nitrite/nitrate levels and neuroinflammation in amygdala. Chronic SBS was associated with long term cognitive damage. Microglial activation showed to be involved with SBS, neuroinflammation and cognitive damage. Conclusion: Physiological alterations of sickness behavior are associated with inflammation markers and damage to CNS. Being this protocol of behavioral evaluation help the analysis of CNS alterations and pathways involved in sepsis.Introdução: Alterações comportamentais e fisiológicas ocorrem em resposta ao processo inflamatório, caracterizadas como comportamento doentio. A sepse é uma resposta inflamatória sistêmica exacerbada devido à infecção, gerando consequências em diversos órgãos, inclusive ao cérebro, causando alterações neurológicas e dano cognitivo. Objetivo: Investigar o comportamento doentio e o envolvimento da neuroinflamação e dano cognitivo na sepse experimental. Métodos: Ratos Wistar machos de dois meses de vida foram submetidos ao modelo de sepse por ligação e perfuração cecal (grupo CLP) ou somente laparotomia (grupo sham). Os animais foram avaliados para a presença do comportamento doentio no momento da indução da sepse, 6h, 12h e 24h após, para avaliação aguda da neuroinflamação e dano à barreira hematoencefálica (BHE) nas estruturas amígdala, núcleo accumbens, hipocampo e córtex pré-frontal em 24h após CLP. Ou diariamente durante oito dias nos experimentos para avaliação a longo prazo da neuroinflamação e dano cognitivo. Sendo o comportamento doentio determinado pelos seguintes critérios: hipotermia, anorexia, adipsia, anedonia e letargia. Foi estabelecida a escala de comportamento doentio (SBS) a partir da alteração do comportamento saudável dos animais prévio à sepse. Também foi avaliado o envolvimento da ativação microglial, através da inibição da micróglia M1 com o uso da minociclina. Resultados: Os animais do grupo CLP apresentaram comportamento doentio acentuado agudo e crônico. Foi observada uma associação entre SBS e dano a BHE, citocina IL-6, corticosterona, BDNF, níveis de nitrito/nitrato e alterações neuroinflamatórias na amígdala. Bem como foi associado os níveis de SBS a longo prazo com o dano cognitivo. A ativação microglial demonstrou estar envolvida no SBS, neuroinflamação e dano cognitivo. Conclusão: As alterações fisiológicas de comportamento doentio estão associadas a marcadores inflamatórios e de dano no SNC. Podendo este protocolo de avaliação comportamental auxiliar na avaliação de alterações do SNC e investigação de vias relacionadas na sepse.Petronilho, Fabricia CardosoGoldim, Mariana Pereira de Souza2018-12-14T11:52:56Z2020-11-26T20:45:23Z2018-12-14T11:52:56Z2020-11-26T20:45:23Z2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis121 f.application/pdfhttps://repositorio.animaeducacao.com.br/handle/ANIMA/2994Programa de Pós-Graduação em Ciência da SaúdeTubarão/ SCAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessporreponame:Repositório Universitário da Ânima (RUNA)instname:Ânima Educaçãoinstacron:Ânima2020-12-01T16:45:52Zoai:repositorio.animaeducacao.com.br:ANIMA/2994Repositório InstitucionalPRIhttps://repositorio.animaeducacao.com.br/oai/requestcontato@animaeducacao.com.bropendoar:2020-12-01T16:45:52Repositório Universitário da Ânima (RUNA) - Ânima Educaçãofalse
dc.title.none.fl_str_mv Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
title Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
spellingShingle Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
Goldim, Mariana Pereira de Souza
Comportamento doentio
Sepse
Neuroinflamação
title_short Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
title_full Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
title_fullStr Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
title_full_unstemmed Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
title_sort Estudo do comportamento doentio na sepse experimental e o envolvimento da disfunção cerebral e ativação microglial
author Goldim, Mariana Pereira de Souza
author_facet Goldim, Mariana Pereira de Souza
author_role author
dc.contributor.none.fl_str_mv Petronilho, Fabricia Cardoso
dc.contributor.author.fl_str_mv Goldim, Mariana Pereira de Souza
dc.subject.por.fl_str_mv Comportamento doentio
Sepse
Neuroinflamação
topic Comportamento doentio
Sepse
Neuroinflamação
description Introduction: Behavioral and physiological alterations occur due inflammatory process, called as sickness behavior. Sepsis is an overwhelmed systemic inflammation response due an infection, leading to organ damage, including brain, causing neurological alterations and cognitive brain damage. Objective: Investigate sickness behavior and its involvement with neuroinflammation and cognitive damage in experimental sepsis. Methods: Male Wistar rats of two months of age were submitted to sepsis model of cecal ligation and puncture (CLP group) or laparotomy only (sham group). Sickness behavior were evaluated prior surgery, 6h, 12h and 24h after, for analysis of acute neuroinflammation and blood-brain barrier (BBB) leakage at brain structures: amygdala, nucleus accumbens, hippocampus and prefrontal cortex at 24h after CLP. Or daily evaluations during eight days for analysis of long term neuroinflammation and cognitive damage. Sickness behavior were determined by the following criteria: hypothermia, anorexia, adipsia, anhedonia and lethargy. The sickness behavior score (SBS) were determined by the alteration of healthy behavior prior sepsis. Also, were evaluated the involvement of microglia activation, by inhibition of M1 microglia by minocycline. Results: CLP animals showed increased sickness behavior in acute and chronic evaluation. It was observed an association of SBS and BBB leakage, IL-6 cytokine, corticosterone, BDNF, nitrite/nitrate levels and neuroinflammation in amygdala. Chronic SBS was associated with long term cognitive damage. Microglial activation showed to be involved with SBS, neuroinflammation and cognitive damage. Conclusion: Physiological alterations of sickness behavior are associated with inflammation markers and damage to CNS. Being this protocol of behavioral evaluation help the analysis of CNS alterations and pathways involved in sepsis.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-14T11:52:56Z
2018-12-14T11:52:56Z
2018
2020-11-26T20:45:23Z
2020-11-26T20:45:23Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.animaeducacao.com.br/handle/ANIMA/2994
url https://repositorio.animaeducacao.com.br/handle/ANIMA/2994
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv Programa de Pós-Graduação em Ciência da Saúde
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nc-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nc-nd/3.0/br/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 121 f.
application/pdf
dc.coverage.none.fl_str_mv Tubarão/ SC
dc.source.none.fl_str_mv reponame:Repositório Universitário da Ânima (RUNA)
instname:Ânima Educação
instacron:Ânima
instname_str Ânima Educação
instacron_str Ânima
institution Ânima
reponame_str Repositório Universitário da Ânima (RUNA)
collection Repositório Universitário da Ânima (RUNA)
repository.name.fl_str_mv Repositório Universitário da Ânima (RUNA) - Ânima Educação
repository.mail.fl_str_mv contato@animaeducacao.com.br
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