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


METHODS
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'.


RESULTS
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-kappaB 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.


CONCLUSIONS
Agents with anti-inflammatory activity (particularly anti- NF-kappaB effects) have potential as therapeutic drugs for CAs.
Kyoto University, Pharmacology, Kyoto 606-8507, Japan.
Tomohiro
T
Aoki
M
M
Nishimura
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D002532:Intracranial Aneurysm / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000209:etiology / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B