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Brain Endothelial Cell Death: Modes, Signaling Pathways, and Relevance to Neural Development, Homeostasis, and Disease

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Abstract

Emerging evidence indicates that brain microvascular endothelial cells play a critical role in brain development, maturation, and homeostasis. Acute or chronic insults, including oxidative stress, oxygen–glucose deprivation, trauma, infections, inflammatory cytokines, DNA damaging agents, β-amyloid deposition, and endoplasmic reticulum stress induce brain endothelial cell dysfunction and damage, which can result in cell death. The homeostatic balance between endothelial cell survival and endothelial cell death is critical for brain development, remodeling, and repair. On the other hand, dysregulation of brain endothelial cell death exacerbates, or even initiates, several inflammatory, ischemic, and degenerative disorders of the central nervous system. In here, the morphological, biochemical, and functional characteristics of the brain endothelium and its contribution to brain homeostasis will be reviewed. Recent insights into modalities and regulatory pathways involved in brain endothelial cell death will be described. The effects of regulated and dysregulated endothelial cell death leading to angiogenesis will be outlined. The relevance of brain endothelial cell dysfunction and death to disease processes will be discussed with special reference to recent findings that could help translate current knowledge on brain endothelial cell apoptosis into new therapeutic strategies for the treatment of certain neurological disorders.

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Acknowledgments

We thank Shannon Wilson, a volunteer student in M.T.R.’s laboratory, for her assistance during the preparation of this manuscript and Christopher Brown from the Department of Visual Media at Indiana University School of Medicine.

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Authors and Affiliations

  1. Signal Transduction Laboratory, Methodist Research Institute, 1800 N. Capitol, Noyes Bldg, Room E504E, Indianapolis, IN, 46202, USA

    Maria Teresa Rizzo

  2. Department of Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA

    Maria Teresa Rizzo

  3. Department of Clinical Neuroscience, Edinburgh University, Edinburgh, UK

    H. Anne Leaver

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  1. Maria Teresa Rizzo
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  2. H. Anne Leaver
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Correspondence to Maria Teresa Rizzo.

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Rizzo, M.T., Leaver, H.A. Brain Endothelial Cell Death: Modes, Signaling Pathways, and Relevance to Neural Development, Homeostasis, and Disease. Mol Neurobiol 42, 52–63 (2010). https://doi.org/10.1007/s12035-010-8132-6

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  • DOI: https://doi.org/10.1007/s12035-010-8132-6

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