NeuroMolecular Medicine

, Volume 21, Issue 4, pp 325–343 | Cite as

Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms

  • Zhen Xu
  • Yan-Ning Rui
  • John P. HaganEmail author
  • Dong H. KimEmail author
Review Paper


Intracranial aneurysms (IA) are local dilatations in cerebral arteries that predominantly affect the circle of Willis. Occurring in approximately 2–5% of adults, these weakened areas are susceptible to rupture, leading to subarachnoid hemorrhage (SAH), a type of hemorrhagic stroke. Due to its early age of onset and poor prognosis, SAH accounts for > 25% of years lost for all stroke victims under the age of 65. In this review, we describe the cerebrovascular pathology associated with intracranial aneurysms. To understand IA genetics, we summarize syndromes with elevated incidence, genome-wide association studies (GWAS), whole exome studies on IA-affected families, and recent research that established definitive roles for Thsd1 (Thrombospondin Type 1 Domain Containing Protein 1) and Sox17 (SRY-box 17) in IA using genetically engineered mouse models. Lastly, we discuss the underlying molecular mechanisms of IA, including defects in vascular endothelial and smooth muscle cells caused by dysfunction in mechanotransduction, Thsd1/FAK (Focal Adhesion Kinase) signaling, and the Transforming Growth Factor β (TGF-β) pathway. As illustrated by THSD1 research, cell adhesion may play a significant role in IA.


Intracranial aneurysm Subarachnoid hemorrhage Etiology Genetics Animal models THSD1 



This work was supported by the grant # 1R01NS104280-01A1 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health. We thank Dr. Joanna O’Leary for helpful comments that helped improve the manuscript.

Compliance with Ethical Standards

Conflicts of interest

There are no conflicts of interest to report.


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Authors and Affiliations

  1. 1.Department of Neurosurgery, McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonUSA

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