The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

Int J Mol Sci. 2023 Sep 18;24(18):14218. doi: 10.3390/ijms241814218.


Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.

Keywords: NF-κB; animal models; cerebral aneurysm rupture; inflammation; intracranial aneurysm; matrix metalloproteinases; pharmacological treatments.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Arteries
  • Humans
  • Inflammation
  • Intracranial Aneurysm* / etiology
  • NF-kappa B*
  • Signal Transduction


  • NF-kappa B

Grants and funding

Open access funding provided by University of Helsinki. This work was supported by grants from Peek and Cloppenburg Stiftung 2021, BMBF, and Forschungskommission HHU Düsseldorf 2020 and 2022 to S. Muhammad.