Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

Autor:	Yang T; Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC, USA. Electronic address: ting.yang2@duke.edu., Velagapudi R; Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, USA., Kong C; Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, USA., Ko U; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA., Kumar V; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Brown P; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Franklin NO; Department of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, NC, USA., Zhang X; Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, USA., Caceres AI; Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, USA., Min H; Department of Neurosurgery, Duke University, Durham, NC, USA., Filiano AJ; Department of Neurosurgery, Duke University, Durham, NC, USA; Department of Immunology, Duke University Medical Center, Durham, NC, USA., Rodriguiz RM; Department of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, NC, USA., Wetsel WC; Department of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, NC, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC, USA., Varghese S; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA., Terrando N; Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, USA; Department of Immunology, Duke University Medical Center, Durham, NC, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.
Jazyk:	angličtina
Zdroj:	British journal of anaesthesia [Br J Anaesth] 2023 Feb; Vol. 130 (2), pp. e370-e380. Date of Electronic Publication: 2022 Jun 29.
DOI:	10.1016/j.bja.2022.05.025
Abstrakt:	Background: Peripheral 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. Methods: A 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. Results: Omega-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. Conclusions: We 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.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu