• Ting Yang, Ravikanth Velagapudi, Cuicui Kong, Unghyeon Ko, Vardhman Kumar, Paris Brown, Nathan O Franklin, Xiaobei Zhang, Ana I Caceres, Hyunjung Min, Anthony J Filiano, Ramona M Rodriguiz, William C Wetsel, Shyni Varghese, and Niccolò Terrando.
• Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC, USA. Electronic address: ting.yang2@duke.edu.
• Br J Anaesth. 2023 Feb 1; 130 (2): e370e380e370-e380.

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.Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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