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Oxidative Stress and Brain Endothelial Cells

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Systems Biology of Free Radicals and Antioxidants

Abstract

In addition to their role in maintaining the anatomical and functional integrity of the blood–brain barrier (BBB) and hemodynamic regulation of blood flow, brain microvascular endothelial cells critically contribute to brain development and homeostasis. Thus, injuries to the brain microvasculature can have deleterious consequences on the neurovascular unit and play an important role in the pathogenesis of several neurological disorders. Reactive oxygen species (ROS) and proinflammatory lipid mediators released either from endothelial cells or from the surrounding brain parenchyma are implicated in endothelial cell injury and vascular damage as well as in regulation of endothelial cell physiological responses. While ROS can initiate an inflammatory response and target membrane lipids, inflammatory lipid mediators can exacerbate oxidative stress by increasing ROS production or can alternatively limit cell damage by homeostatic feedback reactions. This chapter will review the current information pertaining to the role and mechanisms of ROS-dependent regulation of brain endothelial cell function and dysfunction. The role of arachidonic acid, a biologically active and oxidant sensitive polyunsaturated fatty acid, whose levels dramatically increase during inflammation, on ROS generation and subsequent brain vascular damage, will be discussed. Emphasis will be placed on the signaling cooperation by which ROS and arachidonic acid influence brain endothelial cell responses during oxidative stress and inflammation. The clinical significance of ROS- and arachidonic acid-dependent cellular interactions in regulation of brain endothelial cell responses and the therapeutic implications of targeting their signaling effectors will be discussed.

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Abbreviations

ASK-1:

Apoptosis signal-regulating kinase-1

COX-1:

Cyclooxygenase-1

COX-2:

Cyclooxygenase-2

cPLA2:

Cytosolic phospholipase A2

ERK:

Extracellular signal-regulated kinase

JNK:

c-Jun-N-terminal kinase

NO:

Nitric oxide

NO2:

Nitric dioxide

PGE2 :

Prostaglandin E2

PGG2 :

Hydroperoxy endoperoxide prostaglandin G2

sPLA2:

Secreted phospholipase A2

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We are grateful to Dr. Dino Rotondo for advice on eicosanoid vasoactivity, Professor Ian Whittle for discussion of clinical edema, and Chris Brown for artwork. We regret having to omit the work of many colleagues because of space limitations. The original research findings from our laboratories discussed in this chapter were supported by the American Heart Association, the Showalter Foundation and Institutional Funds to M.T.R., and the Chest, Heart and Stroke Foundation (Scotland) to H.A.L.

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Authors and Affiliations

  1. Signal Transduction Laboratory, Methodist Research Institute and Department of Pharmacology, Indiana University Health and Indiana University School of Medicine, 1800 North Capitol, Noyes Building, Room E504E, Indianapolis, IN, 46202, USA

    Maria Teresa Rizzo

  2. Signal Transduction Laboratory, Methodist Research Institute, Indiana University Health, 1800 North Capitol, Noyes Building, Room E504E, Indianapolis, IN, 46202, USA

    Muhammad Saquib

  3. Division of Neuroscience, Edinburgh University, Edinburgh, UK

    H. Anne Leaver

Authors
  1. Maria Teresa Rizzo
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  2. Muhammad Saquib
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  3. H. Anne Leaver
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Correspondence to Maria Teresa Rizzo .

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Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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© 2014 Springer-Verlag Berlin Heidelberg

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Rizzo, M.T., Saquib, M., Leaver, H.A. (2014). Oxidative Stress and Brain Endothelial Cells. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_93

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