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Immune Cell-Derived Free Radicals in Acute Brain Injury

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Immunological Mechanisms and Therapies in Brain Injuries and Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR,volume 6))

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Abstract

Oxidative stress, which generates reactive oxygen species (ROS), plays an important role after acute brain injuries, including transient cerebral ischemia. Brain injuries like ischemic–reperfusion result in a surge of excess oxygen that leads to generation of free radicals. Free radicals are present at low levels in the normal state where they play a critical role in signaling pathways. Antioxidants help in maintaining the redox level in the cells, but during an insult this homeostasis is disturbed resulting in excessive ROS. Mitochondrial ROS are among the main intracellular ROS. Cerebral ischemia triggers inflammation in response to injury, which also leads to the generation of free radicals and eventually to neuronal cell death. Studies using genetically manipulated animals where antioxidant genes are overexpressed or knocked down show the key role that ROS play in ischemia. Oxidative stress affects the injured area in a multifaceted way. It activates apoptotic markers, inflammatory mediators including cytokines and chemokines, and transcriptional activators. Therefore, it has a significant function in cell death and survival signaling cascades. Several recent reports have demonstrated the various effects of ROS generation and its link to the inflammatory response after ischemia. In this chapter, we present an overview of these mechanisms that have been elucidated, focusing on the damaging effects of ROS and their crucial role in inflammation after stroke.

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Abbreviations

cyt c:

Cytochrome c

DAPI:

4′,6 Diamidino-2-phenylindole

GPx:

Glutathione peroxidase

HEt:

Hydroethidine

HO-1:

Hemoxygenase-1

ICAM1:

Intercellular adhesion molecule 1

IL:

Interleukin

I/R:

Ischemia/reperfusion

MCAO:

Middle cerebral artery occlusion

MCP-1:

Monocyte chemoattractant protein-1

MIP-1α:

Macrophage inflammatory protein-1α

mNSS:

Modified neurologic severity scores

NF-κB:

Nuclear factor-kappa B

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

non-PC:

Non-preconditioned

NOX:

NADPH oxidase

NQO1:

NADH quinone oxidoreductase

NSCs:

Neural stem cells

O2 •ˉ:

Superoxide anion

O.D.:

Optical density

OH:

Hydroxyl ion

ONOO:

Peroxynitrite

PC:

Preconditioned

ROS:

Reactive oxygen species

s.d.:

Standard deviation

siRNA:

Small interfering RNA

SOD:

Superoxide dismutase

STAT3:

Signal transducer and activator of transcription 3

Tg:

Transgenic

TNF-α:

Tumor necrosis factor-α

TUNEL:

Terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling

Wt:

Wild-type

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Acknowledgments

This work was supported by NIH grants PO1 NS014543, RO1 NS025372, and RO1 NS038653, and by the James R. Doty Endowment.

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Authors and Affiliations

  1. Stanford University School of Medicine, Stanford, CA, USA

    Purnima Narasimhan, Hiroyuki Sakata, Joo Eun Jung, Tatsuro Nishi, Takuma Wakai, Carolina M. Maier & Pak H. Chan

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  1. Purnima Narasimhan
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  2. Hiroyuki Sakata
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  3. Joo Eun Jung
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  5. Takuma Wakai
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Corresponding author

Correspondence to Pak H. Chan .

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Editors and Affiliations

  1. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Xiaoming Hu

  3. Molecular Microbiology & Immunology, Oregon Health & Sciences University, Portland, Oregon, USA

    Mary Stenzel-Poore

  4. Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Narasimhan, P. et al. (2014). Immune Cell-Derived Free Radicals in Acute Brain Injury. In: Chen, J., Hu, X., Stenzel-Poore, M., Zhang, J. (eds) Immunological Mechanisms and Therapies in Brain Injuries and Stroke. Springer Series in Translational Stroke Research, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8915-3_4

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  • DOI: https://doi.org/10.1007/978-1-4614-8915-3_4

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