Molecular Basis for Intracranial Aneurysm Formation

  • Miyuki Fukuda
  • Tomohiro AokiEmail author
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 120)


Intracranial aneurysm (IA) is a socially important disease both because it has a high prevalence and because of the severity of resultant subarachnoid hemorrhages after IA rupture. The major concern of current IA treatment is the lack medical therapies that are less invasive than surgical procedures for many patients. The current situation is mostly caused by a lack of knowledge regarding the regulating mechanisms of IA formation. Hemodynamic stress, especially high wall shear stress, loaded on arterial bifurcation sites is recognized as a trigger of IA formation from studies performed in the field of fluid dynamics. On the other hand, many studies using human specimens have also revealed the presence of active inflammatory responses, such as the infiltration of macrophages, in the pathogenesis of IA. Because of these findings, recent experimental studies, mainly using animal models of IA, have revealed some of the molecular mechanisms linking hemodynamic stress and long-lasting inflammation in IA walls. Currently, we propose that IA is a chronic inflammatory disease regulated by a positive feedback loop consisting of the cyclooxygenase (COX)-2 – prostaglandin (PG) E2 – prostaglandin E receptor 2 (EP2) – nuclear factor (NF)-κB signaling pathway triggered under hemodynamic stress and macrophage infiltration via NF-κB-mediated monocyte chemoattractant protein (MCP)-1 induction. These findings indicate future directions for the development of therapeutic drugs for IAs.


Intracranial aneurysm Subarachnoid hemorrhage Inflammation Nuclear factor (NF)-κB Macrophage Prostaglandin Cyclooxygenase-2 (COX-2) EP2 Monocyte chemoattractant protein-1 (MCP-1) Statin 



The authors are grateful to all of the researchers, collaborators, technical assistants, and secretaries contributing to our studies cited in the present manuscript. We also express our sincere gratitude to the grants supporting our research.

Conflict of Interest Statement

 We declare that we have no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of NeurosurgeryKyoto University Graduate School of MedicineKyotoJapan
  2. 2.Department of PharmacologyKyoto University Graduate School of MedicineKyotoJapan
  3. 3.Core Research for Evolutional Science and Technology (CREST)Kyoto University Graduate School of MedicineKyotoJapan
  4. 4.Innovation Center for Immunoregulation Technologies and Drugs (AK Project)Kyoto University Graduate School of MedicineSakyo-ku, Kyoto cityJapan

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