{"doi":"10.1016/j.ebiom.2022.103843","title":"Inhibition of caspase-1-mediated inflammasome activation reduced blood coagulation in cerebrospinal fluid after subarachnoid haemorrhage","abstract":"BACKGROUND: Neuroinflammation and blood coagulation responses in cerebrospinal fluid (CSF) contribute to the poor outcome associated with subarachnoid haemorrhage (SAH). We explored the role of caspase-1-mediated inflammasome activation on extrinsic blood coagulation in CSF after SAH. METHODS: Post-SAH proteomic changes and correlation between caspase-1 with extrinsic coagulation factors in human CSF after SAH were analysed. Time course and cell localisation of brain inflammasome and extrinsic coagulation proteins after SAH were explored in a rat SAH model. Pharmacological inhibition of caspase-1 via VX-765 was used to explore the role of caspase-1 in blood clearance and CSF circulation after SAH in rats. Primary astrocytes were used to evaluate the role of caspase-1 in haemoglobin-induced pyroptosis and tissue factor (TF) production/release. FINDINGS: Neuroinflammation and blood coagulation activated after SAH in human CSF. The caspase-1 levels significantly correlated with the extrinsic coagulation factors. The activated caspase-1 and extrinsic coagulation initiator TF was increased on astrocytes after SAH in rats. VX-765 attenuated neurological deficits by accelerating CSF circulation and blood clearance through inhibiting pyroptotic neuroinflammation and TF-induced fibrin deposition in the short-term, and improved learning and memory capacity by preventing hippocampal neuronal loss and hydrocephalus in the long-term after SAH in rats. VX-765 reduced haemoglobin-induced pyroptosis and TF production/release in primary astrocytes. INTERPRETATION: Inhibition of caspase-1 by VX-765 appears to be a potential treatment against neuroinflammation and blood coagulation in CSF after SAH. FUNDING: This study was supported by National Institutes of Health of United States of America, and National Natural Science Foundation of China.","journal":"EBioMedicine","year":2022,"id":237732,"datarank":0.6166310796259968,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":0.0,"self_endowment_contribution":0.6166310796259968,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":860601,"name":"Xiaoyu Wang","orcid":"0000-0002-4809-9332","position":1,"is_corresponding":false},{"id":860602,"name":"Jianan Lü","orcid":"0000-0002-6383-506X","position":2,"is_corresponding":false},{"id":323388,"name":"Hui Shi","orcid":"0000-0002-0104-8212","position":3,"is_corresponding":false},{"id":247832,"name":"Lei Huang","orcid":"0000-0002-7211-8337","position":4,"is_corresponding":false},{"id":860603,"name":"Anwen Shao","orcid":"0000-0001-9986-6290","position":5,"is_corresponding":false},{"id":860604,"name":"Anke Zhang","orcid":"0000-0002-0007-7724","position":6,"is_corresponding":false},{"id":860605,"name":"Yibo Liu","orcid":"0000-0003-2680-9185","position":7,"is_corresponding":false},{"id":323389,"name":"Reng Ren","orcid":"0000-0002-4458-0559","position":8,"is_corresponding":false},{"id":286450,"name":"Cameron Lenahan","orcid":"0000-0002-2979-7979","position":9,"is_corresponding":false},{"id":247836,"name":"Jiping Tang","orcid":"0000-0002-2392-9280","position":10,"is_corresponding":false},{"id":323395,"name":"Jianmin Zhang","orcid":"0000-0002-3184-1502","position":11,"is_corresponding":false},{"id":231009,"name":"John H. Zhang","orcid":"0000-0002-4319-4285","position":12,"is_corresponding":false},{"id":675059,"name":"Sheng Chen","orcid":"0000-0002-8374-136X","position":13,"is_corresponding":false},{"id":323387,"name":"Yuanjian Fang","orcid":"0000-0002-0035-6045","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:21.693802Z","pmid":"35101655","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":[]}