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Tumor Necrosis Factor-α Modulates Cerebral Aneurysm Formation and Rupture

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Abstract

Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in cerebral aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in cerebral aneurysms.

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Abbreviations

AP:

Activator protein

FADD:

Fas-associated death domain

CIAP:

Cellular FLICE-like inhibitory protein

ICAM-1:

Intercellular adhesion molecule-1

Ikk:

Inhibitor of kB kinase

IL-1B:

Interleukin 1B

IP3R:

Inositol 1,4,5-trisphosphate receptor

JNK:

Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

MEKK:

Mitogen-activated protein kinase kinase

MKK:

Dual specificity mitogen-activated protein kinase kinase

MMP:

Matrix metalloproteinases

NFAT:

Nuclear factor for activated T (NFAT)

NFkB:

Nuclear factor

NO:

Nitric oxide

RIP:

Receptor interacting protein

ROS:

Reactive oxygen species

SM-MHC:

Smooth muscle myosin heavy chain

SM-α-actin:

Smooth muscle alpha actin

SM22α:

Smooth muscle 22 alpha

SMC:

Smooth muscle cells

TNF-α:

Tumor necrosis factor alpha

TNFR:

Tumor necrosis factor receptor

TRADD:

TNFR-associated death domain

TRAF:

TNF receptor-associated factor

VCAM:

Vascular cell adhesion molecule-1

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Funding

This work was supported by the National Institute of Neurological Disorders and Stroke [1K08NS067072 to ASD].

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA

    Robert M. Starke, Daniel M. S. Raper & Dale Ding

  2. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA

    Nohra Chalouhi

  3. Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, Charlottesville, VA, USA

    Gary K. Owens

  4. Department of Neurological Surgery, University of Iowa, Iowa City, IA, USA

    David M. Hasan

  5. Department of Neurological Surgery, Tulane University, 131 S. Robertson St., Suite 1300, New Orleans, LA, USA

    Ricky Medel & Aaron S. Dumont

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  1. Robert M. Starke
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Correspondence to Aaron S. Dumont.

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Starke, R.M., Raper, D.M.S., Ding, D. et al. Tumor Necrosis Factor-α Modulates Cerebral Aneurysm Formation and Rupture. Transl. Stroke Res. 5, 269–277 (2014). https://doi.org/10.1007/s12975-013-0287-9

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