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

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

Publication , Journal Article

Yang, T; Velagapudi, R; Kong, C; Ko, U; Kumar, V; Brown, P; Franklin, NO; Zhang, X; Caceres, AI; Min, H; Filiano, AJ; Rodriguiz, RM ...

Published in: Br J Anaesth

February 2023

Published version (DOI) Link to item

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.

Duke Scholars

Author Anabel De Caceres Bustos

Author Niccolò Terrando Anesthesiology

Author William Christopher Wetsel Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...

Author Ting Yang Medicine, Nephrology

Author Anthony J Filiano Neurosurgery

Author Shyni Varghese Orthopaedic Surgery

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Published In

Br J Anaesth

DOI

10.1016/j.bja.2022.05.025

EISSN

1471-6771

Publication Date

February 2023

Volume

130

Issue

Start / End Page

e370 / e380

Location

England

Related Subject Headings

Vascular Cell Adhesion Molecule-1
Neuroinflammatory Diseases
Mice
Humans
Fatty Acids, Omega-3
Emulsions
Emergence Delirium
Blood-Brain Barrier
Animals
Anesthesiology

Citation

APA

Chicago

ICMJE

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NLM

Yang, T., Velagapudi, R., Kong, C., Ko, U., Kumar, V., Brown, P., … Terrando, N. (2023). Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice. Br J Anaesth, 130(2), e370–e380. https://doi.org/10.1016/j.bja.2022.05.025

Yang, Ting, Ravikanth Velagapudi, Cuicui Kong, Unghyeon Ko, Vardhman Kumar, Paris Brown, Nathan O. Franklin, et al. “Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.” Br J Anaesth 130, no. 2 (February 2023): e370–80. https://doi.org/10.1016/j.bja.2022.05.025.

Yang T, Velagapudi R, Kong C, Ko U, Kumar V, Brown P, et al. Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice. Br J Anaesth. 2023 Feb;130(2):e370–80.

Yang, Ting, et al. “Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.” Br J Anaesth, vol. 130, no. 2, Feb. 2023, pp. e370–80. Pubmed, doi:10.1016/j.bja.2022.05.025.

Yang T, Velagapudi R, Kong C, Ko U, Kumar V, Brown P, Franklin NO, Zhang X, Caceres AI, Min H, Filiano AJ, Rodriguiz RM, Wetsel WC, Varghese S, Terrando N. Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice. Br J Anaesth. 2023 Feb;130(2):e370–e380.