Targeting chronic inflammation in cerebral aneurysms: focusing on NF-κB as a putative target of medical therapy

Abstract

Importance of the field: Cerebral aneurysms (CAs) are the main cause of life-threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA treatment is a public health issue. Effective medical treatment of CAs is lacking because the detailed mechanisms of CA formation are incompletely understood.

Areas covered in this review: The aim of this contribution is to review recent articles about CA formation, to suggest the underlying mechanisms of CA formation, and to discuss potential therapeutic targets for treatment. Articles were collected by an internet search of PubMed using the keywords ‘intracranial’ or ‘cerebral aneurysm’.

What the readers will gain: A review of articles about the pathogenesis of CA formation focusing on inflammation. Recent articles demonstrate that inflammation-related-molecule induction and inflammatory cell infiltration in CA walls and the close relationship between inflammatory responses and CA formation. From studies in experimental models, chronic inflammation triggered primarily by NF-κB activation in endothelial cells and subsequent macrophage infiltration have critical roles in CA formation. Inhibition of inflammation-related molecules in CA walls results in the decreased incidence of CA formation.

Take-home message: Agents with anti-inflammatory activity (particularly anti- NF-κB effects) have potential as therapeutic drugs for CAs.

Keywords::

• cerebral aneurysm
• decoy oligodeoxynucleotide
• free-radical scavenger
• inflammation
• macrophage
• nuclear factor-kappa B
• reactive oxygen species
• statin

Notes

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