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Oxidative Mechanisms of Brain Dysfunction During Sepsis

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Abstract

Oxidative stress has drawn a lot of attention in the past few decades, since it has been reported to participate in the mechanism of many diseases. Therefore, it seemed to be a good rationale to aim oxidative stress on therapeutic research. Sepsis is a complex systemic syndrome characterized by an imbalance between pro- and anti-inflammatory responses to a pathogen; its pathophysiology is a dynamic process which involves components of the immune system, the coagulation pathway, parenchymal cells, and the endocrine and metabolic pathways. It is well characterized that oxidative stress plays a crucial role in sepsis development, but the relation between central nervous system dysfunction and oxidative stress during sepsis is not well understood. Thus, we here summarize the current knowledge on the role of free radicals in the development of brain dysfunction in sepsis focusing on oxidative damage and the redox control of brain inflammatory pathways.

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Abbreviations

AP-1:

Activator protein-1

ARE:

Antioxidant response element

ATP:

Adenosine triphosphate

BBB:

Blood-brain-barrier

CAT:

Catalase

CLP:

Cecal ligation and perforation

CNS:

Central nervous system

DNA:

Deoxyribonucleic acid

ERK:

Extracellular signal-regulated kinase

ETC:

Electron transport chain

H2O2 :

Hydrogen peroxide

IKK:

NF-κB (IκB)-kinase

IL-1:

Interleukin-1

IL-1RA:

Interleukin-1 receptor antagonist

IL-1β:

Interleukin-1β

IL-2:

Interleukin-2

IL-6:

Interleukin-6

iNOS:

Inducible nitric oxide synthase

IRAK1:

Interleukin-1 receptor-associated kinase 1

IRAK4:

Interleukin-1 receptor-associated kinase 4

JNK:

Jun N-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemotactic protein-1

MKP-1:

MAPK phosphatase-1

MMP:

Matrix metalloproteinases

mRNA:

Messenger ribonucleic acid

MyD88:

Myeloid differentiation primary-response protein 88

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-κB:

Nuclear factor kappa-B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NrF2:

Nuclear factor-E2 related factor 2

OXPHOS:

Oxidative phosphorylation

PI3K:

Phosphatidylinositol 3-kinase

PKC:

Protein kinase C

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SE:

Septic encephalopathy

SOD:

Superoxide dismutase

TAK1:

Transforming growth factor-β-activated kinase

TLR:

Toll-like receptors

TNF-α:

Tumor necrosis factor-alpha

TRAF6:

Tumor necrosis factor receptor-associated factor 6

XO:

Xanthine oxidase

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Acknowledgments

We would like to thank UNESC (Brazil), FAPESC (Brazil) and CNPq (Brazil) which supported the studies of our group that are cited in this review.

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Authors and Affiliations

  1. Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Felipe Dal-Pizzol, Cristiane Ritter, Omar J. Cassol-Jr, Gislaine T. Rezin, Fabrícia Petronilho & Emilio L. Streck

  2. Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Felipe Dal-Pizzol, Cristiane Ritter, Omar J. Cassol-Jr, Gislaine T. Rezin, Fabrícia Petronilho, Alexandra I. Zugno, João Quevedo & Emilio L. Streck

  3. Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Alexandra I. Zugno & João Quevedo

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  1. Felipe Dal-Pizzol
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Correspondence to Emilio L. Streck.

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Dal-Pizzol, F., Ritter, C., Cassol-Jr, O.J. et al. Oxidative Mechanisms of Brain Dysfunction During Sepsis. Neurochem Res 35, 1–12 (2010). https://doi.org/10.1007/s11064-009-0043-4

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