Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies

Skvarc, David; Berk, Michael; Byrne, Linda K.; Dean, Olivia; Dodd, Seetal; Lewis, Matthew; Marriott, Andrew; Moore, Eileen M.; Morris, Gerwyn; Page, Richard; Gray, Laura J.

doi:10.1016/j.neubiorev.2017.11.011

Cited by 237 publications

(201 citation statements)

References 294 publications

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“…One of the most important mechanisms is neuroinflammation. 10,11 Preclinical evidence showed that surgical trauma resulted in robust immune cell infiltration, inflammatory cytokine expression, or local glia activation, causing neurotoxicity to the central nerve system. 9,12 Prostaglandin E2 (PGE2) is one of the most popular products of inflammation reaction.…”

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confidence: 99%

PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice

et al. 2018

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confidence: 99%

PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice

et al. 2018

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“…Surgical procedures inevitably produce reactive oxygen species (ROS) [44] in the body. Perioperative BBB dysfunction promotes the entry of inflammatory factors and oxidative species into the brain enabling activation of microglia and vascular endothelial cells by cytokines via surface receptors [9]. These activated microglia in turn release ROS with proinflammatory factors, creating a toxic environment in which neuronal damages are induced [9,45].…”

Section: Reduction Of Oxidative Stressmentioning

confidence: 99%

“…Therefore, prevention and management of POCD are important in clinical practice. Pharmacological interventions and advances in perioperative management are continually devloped, and their implications for POCD have been reviewed elsewhere [9,10]. This article focuses on the use of acupuncture for POCD management.…”

Section: Introductionmentioning

confidence: 99%

Application of Acupuncture to Attenuate Immune Responses and Oxidative Stress in Postoperative Cognitive Dysfunction: What Do We Know So Far?

Zhao

Yeung

et al. 2020

Oxidative Medicine and Cellular Longevity

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Postoperative cognitive dysfunction (POCD) is a common sequela following surgery and hospitalization. The prevention and management of POCD are important during clinical practice. POCD more commonly affects elderly patients who have undergone major surgery and can result in major decline in quality of life for both patients and their families. Acupuncture has been suggested as an effective intervention for many neurological disorders. In recent years, there are increasing interest in the use of acupuncture to prevent and treat POCD. In this review, we summarized the clinical and preclinical evidence of acupuncture on POCD using a narrative approach and discussed the potential mechanisms involved. The experimental details and findings of studies were summarized in tables and analyzed. Most of the clinical studies suggested that acupuncture before surgery could reduce the incidence of POCD and reduce the levels of systematic inflammatory markers. However, their reliability is limited by methodological flaws. Animal studies showed that acupuncture reduced cognitive impairment and the associated pathology after various types of surgery. It is possible that acupuncture modulates inflammation, oxidative stress, synaptic changes, and other cellular events to mitigate POCD. In conclusion, acupuncture is a potential intervention for POCD. More clinical studies with good research design are required to confirm its effectiveness. At the same time, findings from animal studies will help reveal the protective mechanisms, in which systematic inflammation is likely to play a major role.

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“…This process is mainly affected by the bone marrowderived macrophages (BMDMs), which react dually to the microenvironmental cues to initiate the neuroin ammation [11][12][13]. Interaction between peripheral immune and brain ampli es the in ammation in the central nervous system (CNS) [14,15], and the cascade of neuroin ammation induces the synaptic dysfunction and neuronal apoptosis, ultimately impairs the cognitive function [16,17]. On this basis, treatments targeting at reversing neuroin ammation show great potential to be candidate therapies for…”

Section: Introductionmentioning

confidence: 99%

Neuroprotectin D1 Protects Against Postoperative Delirium-like Behaviors in Aged Mice by Regulating Neuroinflammation Induced by Surgical Trauma

Zhou¹,

Wang²,

Li³

et al. 2020

Preprint

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Background Postoperative delirium (POD) is the most common postoperative complication affected elderly patients, yet the underlying mechanism is elusive and without effective therapy. The neuroinflammation hypothesis has been emerging as the pathogenesis of POD. Recently, accumulative evidence has supported the role of specialized proresolving lipid mediators (SPMs) in regulating inflammation. NPD1, a novel member of SPMs, is identified with potent immune-resolvent and neuroprotective effect. We aimed to investigate the role of NPD1 in neuroinflammation and postoperative cognitive function with a mice model of POD. Methods Aged male C57BL/6 mice were subjected to laparotomy under isoflurane anesthesia with NPD1 prophylaxis. The general and memory behaviors were assessed by buried food test, open field test and Y maze test at 6, 9, and 24 hours after the surgery. Expression level of inflammatory cytokines were analyzed by ELISA. The permeability of blood-brain barrier (BBB) was detected by spectrophotometric quantification of extravascular dextran tracer from brain tissue extracts, and the expression of tight junction (TJ) associated proteins by Western blotting. The reactive states of astrocytes and microglia were examined by immunofluorescence. The protective effects of NPD1 was also evaluated through macrophage polarization by flow cytometry, using the bone marrow-derived macrophages cultures. Results NPD1 prophylaxis decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in peripheral blood, hippocampus and prefrontal cortex, and limited the leakage of BBB by increasing the expression of TJ associated proteins. Besides, NPD1 prevented the activation of microglia and astrocytes both in the hippocampus and prefrontal cortex, which resulted in improved general and memory function of mice. Furthermore, NPD1 treatment modulated the inflammatory cytokine profile and promoted the macrophage polarization toward M2 in LPS-stimulated macrophages. Conclusions These findings verify the anti-inflammatory and proresolving activities of NPD1 in the inflammatory milieu both in vivo and in vitro, and provide better insight into the pathophysiology and potential therapy for POD.

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Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies

Cited by 237 publications

References 294 publications

PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice

PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice

Application of Acupuncture to Attenuate Immune Responses and Oxidative Stress in Postoperative Cognitive Dysfunction: What Do We Know So Far?

Neuroprotectin D1 Protects Against Postoperative Delirium-like Behaviors in Aged Mice by Regulating Neuroinflammation Induced by Surgical Trauma

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