{"doi":"10.3389/fstro.2023.1202137","title":"NLRP3 inflammasome inhibition protects against intracranial aneurysm rupture and alters the phenotype of infiltrating macrophages","abstract":"Background: Aneurysmal subarachnoid hemorrhage is a devastating cerebrovascular disease associated with high morbidity and mortality. Macrophage-mediated mural inflammation is a key pathogenic component contributing to aneurysm rupture. Objective: To investigate the effect of pharmacological inhibition of the NLRP3 inflammasome on aneurysm rupture. Methods: Cerebral aneurysms were induced in C57BL/6 mice with a combination of hypertension and an intracranial dose of elastase. Mice were treated with either 40 mg/kg of MCC950 or saline via intraperitoneal injections. Vascular tissue at the circle of Willis was harvested for analysis via immunofluorescent microscopy or qPCR. Results: cells are more common in the aneurysm tissue compared to the normal cerebral vasculature. The mRNA expression of the downstream NLRP3 pathway components caspase-1, IL-1β, and GSDMD is also increased in the aneurysm tissue compared to healthy vessels. There was no difference in the aneurysm formation rate between MCC950- and vehicle-treated mice; however, MCC950 treatment significantly reduced aneurysm rupture rate. There was no difference in systemic blood pressure between both groups. MCC950 treatment also extended the symptom-free survival of mice after aneurysm induction. Mechanistically, NLRP3 inhibition decreased the phenotype polarization of infiltrating macrophages without affecting the total number of macrophages in the vessel wall. Conclusions: Our results indicate that the NLRP3 inflammasome contributes to aneurysm rupture and macrophage polarization within the vessel wall. The NLRP3 pathway is a promising therapeutic target for the development of therapeutics to prevent aneurysmal hemorrhagic stroke.","journal":"Frontiers in Stroke","year":2023,"id":369119,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":698487,"name":"Devan Patel","orcid":"0000-0002-3034-3368","position":1,"is_corresponding":false},{"id":430586,"name":"Kartik Motwani","orcid":"0000-0003-1893-8235","position":2,"is_corresponding":false},{"id":698488,"name":"Brandon Lucke‐Wold","orcid":"0000-0001-6577-4080","position":3,"is_corresponding":false},{"id":633097,"name":"Koji Hosaka","orcid":"0000-0003-0106-4586","position":4,"is_corresponding":false},{"id":633098,"name":"Brian L. Hoh","orcid":"0000-0002-4997-4469","position":5,"is_corresponding":false},{"id":633095,"name":"William Dodd","orcid":"0000-0002-8859-6640","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:15:28.704894Z","pmid":"41541085","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":[]}