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Alterations in Inflammatory Mediators, Oxidative Stress Parameters and Energetic Metabolism in the Brain of Sepsis Survivor Rats

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Abstract

Sepsis is characterized by biochemical alterations in the central nervous system at early times and cognitive impairment at late times after induction in sepsis animal model. In order to understand at least in part the mechanism of disease, we have evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF); oxidative parameters; the activity of the electron transport chain enzymes; and creatine kinase (CK) activity in the brain of sepsis survivor rats 10 days after cecal ligation and perforation (CLP). Male Wistar rats underwent CLP with “basic support” or sham-operated. Ten days after surgery, the animals were killed and prefrontal cortex, cortex, hippocampus, striatum, cerebellum, and CSF were obtained. It was found a decrease in the levels of TNF-α (P = 0.001), IL-1β (P = 0.008), IL-6 (P = 0.038), and IL-10 (P = 0.022) in the CSF; an increase in the TBARS only hippocampus (0.027); an up-regulation in the activity of complex II (P = 0.024), III (P = 0.018), and IV (P = 0.047) only in the prefrontal cortex; a decrease in the CK activity in the cerebellum (P = 0.001) and striatum (P = 0.0001), and an increase in the hippocampus (P = 0.0001) and cortex (P = 0.0001). Oxidative stress and mitochondrial alterations observed during early times in sepsis, persisted up to 10 days after surgery. The cytokines levels during the early times were found at high levels, decreasing to low levels after 10 days. In conclusion, these findings may contribute for a better comprehension of the cognitive damage in sepsis survivor rats.

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Acknowledgments

This research was supported by grants from CNPq (ELS, JQ and FD-P), and UNESC (ELS, JQ and FD-P). ELS, JQ and FD-P are CNPq Research Fellows. CMC is holder of a CNPq Studentship, LSC is holder of a FAPESC studentship and GTR, GS and FP are holders of CAPES studentships.

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Authors and Affiliations

  1. Laboratory of Neurosciences and National Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, PPGCS, UNASAU, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil

    Clarissa M. Comim, Omar J. Cassol-Jr & João Quevedo

  2. Laboratory of Experimental Physiopathology and National Institute for Translational Medicine, Postgraduate Program in Health, Sciences, Health Sciences Unit, PPGCS, UNASAU, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil

    Omar J. Cassol-Jr, Larissa S. Constantino, Francine Felisberto, Fabricia Petronilho, Gislaine T. Rezin, Giselli Scaini, Juliana F. Daufenbach, Emilio L. Streck & Felipe Dal-Pizzol

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  1. Clarissa M. Comim
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  2. Omar J. Cassol-Jr
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  3. Larissa S. Constantino
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  6. Gislaine T. Rezin
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  7. Giselli Scaini
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  10. João Quevedo
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  11. Felipe Dal-Pizzol
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Correspondence to João Quevedo.

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Comim, C.M., Cassol-Jr, O.J., Constantino, L.S. et al. Alterations in Inflammatory Mediators, Oxidative Stress Parameters and Energetic Metabolism in the Brain of Sepsis Survivor Rats. Neurochem Res 36, 304–311 (2011). https://doi.org/10.1007/s11064-010-0320-2

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