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

Yang, Ting; Velagapudi, Ravikanth; Kong, Chao; Ko, Unghyeon; Kumar, Vardhman; Brown, Paris; Franklin, Nathan O; Zhang, Xiaobei; Caceres, Ana I.; Min, Hyun Jin; Filiano, Anthony J.; Rodriguiz, Ramona M.; Wetsel, William C.; Varghese, Shyni; Terrando, Niccolò

doi:10.1016/j.bja.2022.05.025

Cited by 21 publications

(25 citation statements)

References 45 publications

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“…Astrocytes are also important regulators of the BBB ( Kadry et al, 2020 ). In this study, we confirmed the loss of astrocytic end-feet processes and endothelial markers at 24 h after surgery in mice, suggesting that BBB opening is a major culprit for ensuing delirium-like behavior ( Yang, 2022 ). Here, we confirmed the validity of another plasma biomarker that is upregulated in delirious subjects: NfL ( Casey et al, 2019 ; Fong et al, 2020 ).…”

Section: Discussionsupporting

confidence: 74%

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Conserved YKL-40 changes in mice and humans after postoperative delirium

David-Bercholz

Acker

Caceres

et al. 2022

Brain, Behavior, & Immunity - Health

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Section: Discussionsupporting

confidence: 74%

“…In particular, we have focused on inattention as one of the key clinical domains ( Velagapudi et al, 2019 ; Wang et al, 2020 ). In addition, our murine model has revealed changes in blood-brain barrier (BBB) permeability after surgery ( Yang, 2022 ), a complication that has now been observed in the clinic ( Taylor et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Conserved YKL-40 changes in mice and humans after postoperative delirium

David-Bercholz

Acker

Caceres

et al. 2022

Brain, Behavior, & Immunity - Health

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“…By using BBB models and animal experiments, Yang et al (2023) confirmed that omega-3 fatty acids can regulate endothelial structure and permeability. Omega-3 fatty acid supplementation can relieve pericyte dysfunction and BBB damage ( Yang et al, 2023 ). In general, the specific effects of perioperative anesthesia and surgical exposure on endothelial cells and pericytes, as well as the specific process and molecular mechanism of BBB permeability changes, have yet to be clarified.…”

Section: Potential Pathophysiological Processes and Mechanismsmentioning

confidence: 81%

“…Therefore, pericyte dysfunction may lead to changes in permeability and BBB disruption (Zheng et al, 2020). By using BBB models and animal experiments, Yang et al (2023) confirmed that omega-3 fatty acids can regulate endothelial structure and permeability. Omega-3 fatty acid supplementation can relieve pericyte dysfunction and BBB damage (Yang et al, 2023).…”

Section: Increased Bbb Permeabilitymentioning

confidence: 83%

Research progress on perioperative blood-brain barrier damage and its potential mechanism

Qiu

et al. 2023

Front. Cell Dev. Biol.

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The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

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“…One mechanism potentially underlying postoperative delirium is blood-brain barrier dysfunction, since animal models of postoperative delirium-like behavior exhibit significant blood-brain dysfunction. [6][7][8] The blood-brain barrier contains non-fenestrated brain capillaries that restrict the free diffusion of solutes and cells into the central nervous system (CNS), which normally protects the CNS from peripheral toxins, pathogens, and inflammation. Although many neurologic diseases include blood-brain barrier dysfunction, including multiple sclerosis, 9 cerebrovascular injury, 10 and Alzheimer's disease, 11 its role in postoperative delirium is unclear.…”

Section: Introductionmentioning

confidence: 99%

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults

Devinney

Wong

Wright

et al. 2023

Preprint

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Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, the role of postoperative blood-brain barrier dysfunction in postoperative delirium and overall recovery is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling was prospectively performed before and after non-cardiac, non-neurologic surgery in older adults. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). Results: Of 207 patients with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median postoperative change 0.28, [IQR] [-0.48- 1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (OR, 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (incidence rate ratio, 1.15 [95% CI 1.09-1.22]; p<0.001) Interpretation: These data demonstrate that postoperative increases in blood-brain barrier permeability are associated with increased delirium risk and increased postoperative hospital length of stay. Although these findings do not establish causality, they suggest studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium risk and hospital length of stay.

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

Cited by 21 publications

References 45 publications

Conserved YKL-40 changes in mice and humans after postoperative delirium

Conserved YKL-40 changes in mice and humans after postoperative delirium

Research progress on perioperative blood-brain barrier damage and its potential mechanism

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults

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