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Acute Brain Inflammation and Oxidative Damage Are Related to Long-Term Cognitive Deficits and Markers of Neurodegeneration in Sepsis-Survivor Rats

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Abstract

Survivors from sepsis present long-term cognitive deficits and some of these alterations resemble the pathophysiological mechanisms of neurodegenerative diseases. For this reason, we analyzed beta-amyloid peptide (Aβ) and synaptophysin levels in the brain of rats that survived from sepsis and their relation to cognitive dysfunction and to acute brain inflammation. Sepsis was induced in rats by cecal ligation and puncture, and 30 days after surgery, the hippocampus and prefrontal cortex were isolated just after cognitive evaluation by the inhibitory avoidance test. The immunocontent of Aβ and synaptophysin were analyzed by Western blot analysis. Aβ increased and synaptophysin decreased in septic animals both in the hippocampus and prefrontal cortex concurrent with the presence of cognitive deficits. Prefrontal levels of synaptophysin correlated to the performance in the inhibitory avoidance. Two different treatments known to decrease brain inflammation and oxidative stress when administered at the acute phase of sepsis decreased Aβ levels both in the prefrontal cortex and hippocampus, increased synaptophysin levels only in the prefrontal cortex, and improved cognitive deficit in sepsis-survivor animals. In conclusion, we demonstrated that brain from sepsis-survivor animals presented an increase in Aβ content and a decrease in synaptophysin levels and cognitive impairment. These alterations can be prevented by treatments aimed to decrease acute brain inflammation and oxidative stress.

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Acknowledgments

The authors declare no conflict of interest. This work was funded by NENASC project (PRONEX program CNPq/FAPESC), INCT-TM, and PROCAD Sepse-CAPES.

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Authors and Affiliations

  1. Laboratório de Fisiopatologia Experimental and Instituto Nacional de Ciência e Técnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, Criciúma, 88006-000, Santa Catarina, Brazil

    Mágada T. Schwalm, Francieli Vuolo, Cristiane Ritter & Felipe Dal-Pizzol

  2. Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Matheus Pasquali, João Paulo A. dos Santos, Daniel P. Gelain & José Cláudio F. Moreira

  3. Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul Catarinense, Tubarão, Santa Catarina, Brazil

    Samantha P. Miguel & Fabrícia Petronilho

  4. Laboratório de Neurociência and Instituto Nacional de Ciência e Técnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil

    Clarissa M. Comim & João Quevedo

Authors
  1. Mágada T. Schwalm
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  2. Matheus Pasquali
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  3. Samantha P. Miguel
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  4. João Paulo A. dos Santos
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  5. Francieli Vuolo
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  6. Clarissa M. Comim
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  7. Fabrícia Petronilho
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  8. João Quevedo
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  9. Daniel P. Gelain
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  10. José Cláudio F. Moreira
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  11. Cristiane Ritter
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  12. Felipe Dal-Pizzol
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Correspondence to Felipe Dal-Pizzol.

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Schwalm, M.T., Pasquali, M., Miguel, S.P. et al. Acute Brain Inflammation and Oxidative Damage Are Related to Long-Term Cognitive Deficits and Markers of Neurodegeneration in Sepsis-Survivor Rats. Mol Neurobiol 49, 380–385 (2014). https://doi.org/10.1007/s12035-013-8526-3

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  • DOI: https://doi.org/10.1007/s12035-013-8526-3

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