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Investigação pré-clínica do impacto da exposição à endotoxina no período neonatal sobre o dano cerebral após a sepse na idade adulta

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Previous issue date: 2015 / Introducao: A sepse e uma importante complicacao infecciosa na area da saude, tanto para sua incidencia e severidade, bem como para o seu potencial de progressao a morte. Estrategias futuras de tratamento podem se concentrar no equilibrio entre as acoes imunes e antiinflamatorias em tempo habil. Objetivo: Avaliar a influencia da administracao de lipolissacarideo (LPS) no periodo neonatal sobre a disfuncao cerebral em ratos submetidos a sepse polimicrobiana severa na idade adulta. Metodos: Ratos Wistar machos com idade de 14 dias foram tratados com LPS (100 ¿Êg/kg) ou salina, intraperitoneal. Completando 60 dias de idade, foram submetidos ao modelo de sepse por ligacao e perfuracao cecal (CLP). Os grupos foram divididos em salina+sham, LPS+sham, salina+CLP e LPS+CLP, 24 horas apos CLP, foi avaliado no liquido cefalorraquidiano (LCR), as citocinas (TNF-¿¿, IL-1¿À e IL-6) os niveis de nitrito e nitrato (N/N). No hipocampo e cortex pre-frontal foi avaliado a mieloperoxidase (MPO), dano oxidativo em lipidios (TBARS), proteinas carboniladas,grupamentos sulfidrilas (SH), atividade da catalase (CAT), superoxido dismutase (SOD) e a permeabilidade da barreira hematoencefalica (BHE). Resultados: Demonstrou-se que os niveis de citocinas e de N/N estao aumentados no grupo CLP e o LPS foi eficaz em reduzir somente os niveis de citocinas. Na MPO e grupamentos SH, nao foram observados resultados significativos. No dano em lipidios e proteinas encontrou-se no pre-frontal um aumento dos niveis no grupo CLP, em ratos pre-imunizados com LPS houve uma diminuicao desses niveis. Na atividade das enzimas antioxidantes, houve uma diminuicao dos niveis somente na CAT, no hipocampo, no grupo imunizado. Para a quebra da BHE, houve um aumento nos grupos CLP, o grupo imunizado diminuiu seus niveis, no pre-frontal. Conclusao: O pre-tratamento com LPS preveniu o dano de marcadores ligados a inflamacao e ao estresse oxidativo, e diminuiu a permeabilidade da BHE apos a sepse na idade adulta. / Introduction: The sepsis is an important infectious complication in the health area, both for its incidence and severity, and for its potential of progression to death. Future strategies of treatment can concentrate on the balance among the immune and anti-inflammatory actions in time. Aim: Evaluate the influence of the administration of lipopolysaccharide (LPS) in the neonatal period over the brain dysfunction in rats submitted to severe polymicrobial sepsis at adult age. Methods: Male Wistar rats at 14 days of age treated with LPS (100 ìg/kg) or saline, intraperitoneal. At 60 days of age, the rats were submitted to the sepsis model by cecal ligation puncture (CLP). The groups were divided in saline+sham, LPS+sham, saline+CLP and LPS+CLP, 24 hours after CLP, the cerebrospinal fluid (CSF) was evaluated, besides the cytokines (TNF-á, IL-1â e IL-6) and the levels of nitrite and nitrate (N/N). On hippocampus and prefrontal cortex was evaluated the myeloperoxidase (MPO), oxidative damage to lipids (TBARS), carbonyl proteins, sulfhydryl groups (SH), catalase activity (CAT), superoxide dismutase (SOD) and the permeability of the blood-brain barrier (BBB). Results: We have demonstrated that the cytokine levels and N/N are increasing in the group CLP and LPS was effective in reduce only the cytokine levels. In MPO and SH groups, we have not observed significant results. In the damage to lipids and proteins, we have found in the prefrontal an increase of the levels in the group CLP and in rats preimmunized with LPS there was a decrease of these levels. In the activity of the antioxidant enzymes there was a reversal of the levels only in CAT, in the hippocampus, in the immunized group. For the breaking of BHE, there was an increase in the groups CLP, the immunized group decreased its levels, in the prefrontal. Conclusion: The pretreatment with LPS prevented the damage of markers connected to inflammation and oxidative stress, and decreased the permeability of BBB after the sepsis at adult age.

Identiferoai:union.ndltd.org:IBICT/oai:riuni.unisul.br:12345/529
Date January 2015
CreatorsFlorentino, Drielly Silva
ContributorsPetronilho, Fabrícia Cardoso
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Sourcereponame:Repositório Institucional da UNISUL, instname:Universidade do Sul de SC, instacron:UNISUL
Rightsinfo:eu-repo/semantics/openAccess

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