{"doi":"10.3390/jcm14228256","title":"Mechanisms of Intracranial Aneurysm Rupture: An Integrative Review of Experimental and Clinical Evidence","abstract":"<jats:p>Background: Intracranial aneurysm (IA) rupture is a devastating event in neurosurgery and a leading cause of subarachnoid hemorrhage. Although aneurysm size has been traditionally emphasized, recent research has highlighted multifactorial mechanisms involving hemodynamic stress, wall degeneration, inflammation, and genetic predisposition. Methods: Evidence from animal models, human pathological studies, computational fluid dynamics analyses, genetic association studies, and advanced imaging research was reviewed to provide an integrated view of rupture mechanisms. Results: Morphological and hemodynamic studies have shown that high aspect and size ratios, coupled with low wall shear stress and an elevated oscillatory shear index, contribute to focal wall weakening. Histopathological analyses of ruptured aneurysms consistently reveal endothelial loss, smooth-muscle-cell depletion, extracellular matrix degradation, and intense inflammatory cell infiltration, with patterns such as extremely thin, hypocellular, thrombosis-lined walls. Experimental studies have identified active inflammatory pathways, including neutrophil-driven cascades via CXCL1 signaling and complement C5a–C5aR1 activation, as direct triggers of wall failure. High-resolution vessel-wall magnetic resonance imaging correlates contrast enhancement with histological evidence of inflammation and neovascularization, suggesting its utility as a biomarker of instability. Conclusions: IA rupture is driven by a dynamic interplay between adverse hemodynamic environments, inflammatory degeneration, genetic susceptibility, and pathological vascular remodeling. Integrating these mechanistic insights may improve risk stratification and guide the development of targeted preventive strategies.</jats:p>","journal":"Journal of Clinical Medicine","year":2025,"id":643011,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":296255,"name":"Tomohiro Aoki","orcid":"0000-0001-6782-8361","position":1,"is_corresponding":false},{"id":1672822,"name":"Masahiko Itani","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mechanisms of Intracranial Aneurysm Rupture: An Integrative Review of Experimental and Clinical Evidence","abstract":"<jats:p>Background: Intracranial aneurysm (IA) rupture is a devastating event in neurosurgery and a leading cause of subarachnoid hemorrhage. Although aneurysm size has been traditionally emphasized, recent research has highlighted multifactorial mechanisms involving hemodynamic stress, wall degeneration, inflammation, and genetic predisposition. Methods: Evidence from animal models, human pathological studies, computational fluid dynamics analyses, genetic association studies, and advanced imaging research was reviewed to provide an integrated view of rupture mechanisms. Results: Morphological and hemodynamic studies have shown that high aspect and size ratios, coupled with low wall shear stress and an elevated oscillatory shear index, contribute to focal wall weakening. Histopathological analyses of ruptured aneurysms consistently reveal endothelial loss, smooth-muscle-cell depletion, extracellular matrix degradation, and intense inflammatory cell infiltration, with patterns such as extremely thin, hypocellular, thrombosis-lined walls. Experimental studies have identified active inflammatory pathways, including neutrophil-driven cascades via CXCL1 signaling and complement C5a–C5aR1 activation, as direct triggers of wall failure. High-resolution vessel-wall magnetic resonance imaging correlates contrast enhancement with histological evidence of inflammation and neovascularization, suggesting its utility as a biomarker of instability. Conclusions: IA rupture is driven by a dynamic interplay between adverse hemodynamic environments, inflammatory degeneration, genetic susceptibility, and pathological vascular remodeling. Integrating these mechanistic insights may improve risk stratification and guide the development of targeted preventive strategies.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41303289","pmcid":"PMC12653054","openalex_id":"https://openalex.org/W4416422207","authors":[],"funders":[{"funder_name":"the grants from the Jikei University School of Medicine","grant_id":"2025-101-SS and 2025-203-HK for T.A.","title":null},{"funder_name":"the grant from SENSHIN Medical Research Foundation","grant_id":"N/A","title":null},{"funder_name":"Japan Society for the Promotion of Science","grant_id":"22H00584, T.A.","title":null}],"total_grants":3,"fwci":3.725,"citation_percentile":0.94040569,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2077-0383/14/22/8256/pdf","host_type":"journal"},{"url":"https://www.mdpi.com/2077-0383/14/22/8256/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/jcm14228256","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41303289","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12653054","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12653054?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Intracranial Aneurysms: Treatment and Complications","Cerebrospinal fluid and hydrocephalus","Intracerebral and Subarachnoid Hemorrhage Research"],"mesh_terms":[],"keywords":["Aneurysm","Hemodynamics","Magnetic resonance imaging","Pathological","Subarachnoid hemorrhage","Inflammation","Extracellular matrix","Neuroradiology","Genetics","Intracranial aneurysm","Rupture Mechanism","Vessel-wall Mri"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T11:43:02.653770Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}