NF-kB as a crucial factor for intracranial aneurysm formation and the potential of statins as drugs for intracranial aneurysm treatment through their anti-NF-kB effect

Introduction Intracranial aneurysm (IA) is a regional bulging of intracranial arteries with degenerative changes in arterial walls. Because IA has a high incidence in general public and can cause subarachnoid haemorrhage, a most severe form of stroke with a high mortality rate, after rupture, treatment of IA is socially important. Nonetheless, to date, there is not any medical treatment available to prevent rupture except for surgical interventions with an unescapable risk of complication. Therefore, development of drugs for IA treatment based on mechanisms of IA formation is socially desired. In the present article, authors will summarize the recent advancement of researches toward the development of drugs for IA treatment. Discussion Findings from human studies and recent experimental studies using rodent models of IAs have proposed the notion that the chronic inflammation mediated by NF-κB activation regulates IA formation and also suggested the potential of NF-κB as therapeutic target for treatment. Indeed, orally administered HMG-CoA reductase inhibitors (statins) exert the excellent inhibitory effect on formation and enlargement of IAs in rodent models through their potent anti-NF-κB effect. Based on these findings, the hospital-based casecontrol study enrolling patients with unruptured or ruptured IAs to examine the effect of statin usage on rupture of IAs in human cases is recently carried out and beneficial effect of statins on rupture of IAs have been revealed. The ratio of statin usage between two groups is significant different and statistically statin usage reduces the risk of rupture of IAs at the adjusted odds ratio of 0.30, suggesting the potential of statins as candidate of drugs for IA treatment to prevent rupture. Conclusion Recent series of experimental and clinical studies greatly promote our understanding of mechanisms underlying IA formation and make a great advancement toward the development of drugs for IA treatment.