Inflammatory Mechanisms in Intracranial Aneurysm Formation, Progression, and Rupture: A Narrative Review

Chronic inflammation contributes to the pathogenesis of intracranial aneurysms (IAs). However, existing studies have generally focused on individual stages of IA pathogenesis. This narrative review synthesizes evidence across all stages of the natural history of IA: formation, progression, and rupture. During formation, aberrant wall shear stress can induce endothelial dysfunction and activate nuclear factor-kappa B (NF-κB) signaling. During progression, NF-κB-driven cytokines, chemokines, and adhesion molecules promote immune-cell recruitment, oxidative stress, vascular smooth muscle cell (VSMC) phenotypic modulation, and extracellular-matrix remodeling. In advanced lesions, persistent inflammation, VSMC loss, and matrix metalloproteinase activity are associated with wall degeneration and rupture. Evidence is derived from complementary experimental models, human aneurysm tissue, and circulating biomarkers; these sources should not be interpreted as equivalent evidence of causality. Circulating inflammatory indices may aid risk stratification but do not directly measure aneurysm-wall inflammation and remain insufficiently validated for clinical decision-making. Better integration of inflammatory, morphological, and hemodynamic information may support future individualized risk assessment and therapeutic development.