{"doi":"10.1016/j.bja.2022.05.025","title":"Protective effects of omega-3 fatty acids in a blood–brain barrier-on-chip model and on postoperative delirium-like behaviour in mice","abstract":"BackgroundPeripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Here, we developed a microfluidic-assisted blood–brain barrier (BBB) device and tested the effects of omega-3 fatty acids on neuroimmune interactions after orthopaedic surgery.MethodsA microfluidic-assisted BBB device was established using primary human cells. Tight junction proteins, vascular cell adhesion molecule 1 (VCAM-1), BBB permeability, and astrocytic networks were assessed after stimulation with interleukin (IL)-1β and in the presence or absence of a clinically available omega-3 fatty acid emulsion (Omegaven®; Fresenius Kabi, Bad Homburg, Germany). Mice were treated 1 h before orthopaedic surgery with 10 μl g−1 body weight of omega-3 fatty acid emulsion i.v. or equal volumes of saline. Changes in pericytes, perivascular macrophages, BBB opening, microglial activation, and inattention were evaluated.ResultsOmega-3 fatty acids protected barrier permeability, endothelial tight junctions, and VCAM-1 after exposure to IL-1β in the BBB model. In vivo studies confirmed that omega-3 fatty acid treatment inhibited surgery-induced BBB impairment, microglial activation, and delirium-like behaviour. We identified a novel role for pericyte loss and perivascular macrophage activation in mice after surgery, which were rescued by prophylaxis with i.v. omega-3 fatty acids.ConclusionsWe present a new approach to study neuroimmune interactions relevant to perioperative recovery using a microphysiological BBB platform. Changes in barrier function, including dysregulation of pericytes and perivascular macrophages, provide new targets to reduce postoperative delirium.","journal":"British Journal of Anaesthesia","year":2022,"id":240014,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"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":272630,"name":"Ravikanth Velagapudi","orcid":null,"position":1,"is_corresponding":false},{"id":269996,"name":"Cuicui Kong","orcid":"0000-0003-4216-2262","position":2,"is_corresponding":false},{"id":867928,"name":"Unghyeon Ko","orcid":null,"position":3,"is_corresponding":false},{"id":793881,"name":"Vardhman Kumar","orcid":"0000-0002-1280-2161","position":4,"is_corresponding":false},{"id":867929,"name":"Paris Brown","orcid":null,"position":5,"is_corresponding":false},{"id":867930,"name":"Nathan O. Franklin","orcid":null,"position":6,"is_corresponding":false},{"id":512972,"name":"Xiaobei Zhang","orcid":"0000-0002-9228-8720","position":7,"is_corresponding":false},{"id":867032,"name":"Ana I. Caceres","orcid":"0000-0001-7219-8851","position":8,"is_corresponding":false},{"id":867033,"name":"Hyunjung Min","orcid":"0009-0002-5823-6780","position":9,"is_corresponding":false},{"id":790777,"name":"Anthony J. Filiano","orcid":"0000-0003-4329-0151","position":10,"is_corresponding":false},{"id":269997,"name":"Ramona M. Rodriguiz","orcid":"0000-0002-4680-9425","position":11,"is_corresponding":false},{"id":258568,"name":"William C. Wetsel","orcid":"0000-0002-3592-7397","position":12,"is_corresponding":false},{"id":619117,"name":"Shyni Varghese","orcid":"0000-0002-0004-7947","position":13,"is_corresponding":false},{"id":270001,"name":"Niccolò Terrando","orcid":"0000-0003-1803-5853","position":14,"is_corresponding":false},{"id":269998,"name":"Ting Yang","orcid":"0000-0002-5113-8611","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:22:46.554789Z","pmid":"35778276","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":[]}