Critical role of TNF-α in cerebral aneurysm formation and progression to rupture

Robert M Starke; Nohra Chalouhi; Pascal M Jabbour; Stavropoula I Tjoumakaris; L Fernando Gonzalez; Robert H Rosenwasser; Kosuke Wada; Kenji Shimada; David M Hasan; Nigel H Greig; Gary K Owens; Aaron S Dumont

doi:10.1186/1742-2094-11-77

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Critical role of TNF-α in cerebral aneurysm formation and progression to rupture

Journal article

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Critical role of TNF-α in cerebral aneurysm formation and progression to rupture

Robert M Starke, Nohra Chalouhi, Pascal M Jabbour, Stavropoula I Tjoumakaris, L Fernando Gonzalez, Robert H Rosenwasser, Kosuke Wada, Kenji Shimada, David M Hasan, Nigel H Greig, …

Journal of neuroinflammation, Vol.11(1), pp.77-77

04/16/2014

DOI: 10.1186/1742-2094-11-77

PMCID: PMC4022343

PMID: 24739142

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Abstract

Background: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. Methods: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining. Results: TNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. Conclusions: These data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

Subarachnoid hemorrhage

TNF-alpha

Tumor necrosis factor

Aneurysm

Rupture

Cerebral

Research

Details

Title: Subtitle: Critical role of TNF-α in cerebral aneurysm formation and progression to rupture
Creators: Robert M Starke - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Nohra Chalouhi - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Pascal M Jabbour - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Stavropoula I Tjoumakaris - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
L Fernando Gonzalez - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Robert H Rosenwasser - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Kosuke Wada - Center for Cerebrovascular Research, University of California San Francisco, San Francisco, CA, USA
Kenji Shimada - Center for Cerebrovascular Research, University of California San Francisco, San Francisco, CA, USA
David M Hasan - Department of Neurosurgery, University of Iowa, Cedar Rapids, IA, USA
Nigel H Greig - National Institute on Aging, National Institutes of Health Translational Gerontology Branch, Intramural Research Program, District of Columbia, USA
Gary K Owens - Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
Aaron S Dumont - Joseph and Marie Field Cerebrovascular Research Laboratory, Division of Neurovascular and Endovascular Surgery, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA
Resource Type: Journal article
Publication Details: Journal of neuroinflammation, Vol.11(1), pp.77-77
DOI: 10.1186/1742-2094-11-77
PMID: 24739142
PMCID: PMC4022343
NLM abbreviation: J Neuroinflammation
ISSN: 1742-2094
eISSN: 1742-2094
Publisher: BioMed Central
Language: English
Date published: 04/16/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurosurgery; Otolaryngology
Record Identifier: 9984040349502771

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