Neuroinflammation: effect of surgical stress compared to anaesthesia and effect of physostigmine

Plaschke, Konstanze; Weigand, Markus; Fricke, Fabia; Kopitz, Jürgen

doi:10.1080/01616412.2016.1173889

Cited by 8 publications

(10 citation statements)

References 41 publications

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“…Plaschke et al have demonstrated that cholinergic signalling mediates the secretion of pro-inflammatory markers, such as IL-1β, following surgical stress [ 45 ], whilst decreases in cerebral acetylcholine results in an increased secretion of numerous pro-inflammatory cytokines [ 46 ]. Furthermore, increasing acetylcholine levels by inhibiting acetylcholinesterase causes a sustained anti-inflammatory effect, which may be a therapeutic option in reducing post-surgical neuroinflammation [ 47 ].…”

Section: Consequences Of Neuroinflammationmentioning

confidence: 99%

“…Adverse events are also common; these include increased length of hospital stay and associated healthcare costs, and increased mortality. Whilst anaesthesia has classically been considered the major contributor to post-operative delirium, animal studies indicate that surgery-induced inflammation may be a significant cause of POD-associated neurological impairment [ 45 , 47 ].…”

Section: Post-surgical Neuroinflammation Related Neuro-disordersmentioning

confidence: 99%

“…The proposed mechanism involves the modulation of nuclear factor-kappa B (NF-κB) activity in monocytes, as well as the attenuation of oxidative stress responses by downregulating nicotinamide adenine dinucleotide phosphate's (NADPH) signalling [ 108 ], and the eventual inhibition of TNF- α [ 37 ]. Furthermore, it has been suggested that utilising procholinergic drugs, such as physostigmine, may also be therapeutic options in downregulating SIRS and neuroinflammation [ 45 , 47 ].…”

Section: Therapeutic Options For Post-operative Neurological Complicamentioning

confidence: 99%

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Surgery, neuroinflammation and cognitive impairment

et al. 2018

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Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Various pro-inflammatory cytokines, such as TNFα, maintain a state of chronic neuroinflammation, manifesting as post-operative cognitive dysfunction and post-operative delirium. Furthermore, elderly patients with post-operative cognitive dysfunction or delirium are three times more likely to experience permanent cognitive impairment or dementia. We conducted a narrative review, considering evidence extracted from various databases including Pubmed, MEDLINE and EMBASE, as well as journals and book reference lists. We found that further pre-clinical and well-powered clinical studies are required to delineate the precise pathogenesis of post-operative delirium and cognitive dysfunction. Despite the burden of post-operative neurological sequelae, clinical studies investigating therapeutic agents, such as dexmedetomidine, ibuprofen and statins, have yielded conflicting results. In addition, evidence supporting novel therapeutic avenues, such as nicotinic and HMGB-1 targeting and remote ischaemic pre-conditioning, is limited and necessitates further investigation.

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Section: Consequences Of Neuroinflammationmentioning

confidence: 99%

Section: Post-surgical Neuroinflammation Related Neuro-disordersmentioning

confidence: 99%

Section: Therapeutic Options For Post-operative Neurological Complicamentioning

confidence: 99%

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Surgery, neuroinflammation and cognitive impairment

et al. 2018

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“…Humoral pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), have been reported to be associated with the leakage of the blood-brain barrier (BBB), which leads to the entry of pro-inflammatory cytokines and monocyte-derived macrophages, resulting in the activation of glia, including microglia and astroglia (Terrando et al, 2011;Hu et al, 2018). The interaction between the peripheral and central immune systems amplifies inflammation in the brain (D'Mello et al, 2009;Perry and Teeling, 2013), and the cascade of neuroinflammation induces synaptic dysfunction and neuronal apoptosis, which ultimately impairs cognitive function (Munster et al, 2011;Plaschke et al, 2016;Skvarc et al, 2018). On this basis, treatments targeting the regulation of neuroinflammation show great potential as candidate therapies for POD.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotectin D1 Protects Against Postoperative Delirium-Like Behavior in Aged Mice

Zhou

Wang

et al. 2020

Front. Aging Neurosci.

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Postoperative delirium (POD) is the most common postoperative complication affecting elderly patients, yet the underlying mechanism is elusive, and effective therapies are lacking. The neuroinflammation hypothesis for the pathogenesis of POD has recently emerged. Accumulating evidence is supporting the role of specialized proresolving lipid mediators (SPMs) in regulating inflammation. Neuroprotectin D1 (NPD1), a novel docosahexaenoic acid (DHA)-derived lipid mediator, has shown potent immunoresolvent and neuroprotective effects in several disease models associated with inflammation. Here, using a mouse model of POD, we investigated the role of NPD1 in postoperative cognitive impairment by assessing systemic inflammatory changes, the permeability of the blood-brain barrier (BBB), neuroinflammation, and behavior in aged mice at different time points. We report that a single dose of NPD1 prophylaxis decreased the expression of tumor necrosis factor alpha TNF-α and interleukin (IL)-6 and upregulated the expression of IL-10 in peripheral blood, the hippocampus, and the prefrontal cortex. Additionally, NPD1 limited the leakage of the BBB by increasing the expression of tight junction (TJ)-associated proteins such as ZO-1, claudin-5, and occludin. NPD1 also abolished the activation of microglia and astrocytes in the hippocampus and prefrontal cortex, which is associated with improved general and memory function after surgery. In addition, NPD1 treatment modulated the inflammatory cytokine expression profile and improved the expression of the M2 marker CD206 in lipopolysaccharide (LPS)stimulated macrophages, which may partly explain the beneficial effects of NPD1 on inflammation. Collectively, these findings shed light on the proresolving activities of NPD1 in the pro-inflammatory milieu both in vivo and in vitro and may bring a novel therapeutic approach for POD.

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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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Neuroinflammation: effect of surgical stress compared to anaesthesia and effect of physostigmine

Abstract: We show in this observational study that a single intraoperative dose of physostigmine produced a sustained anti-inflammatory effect in rat blood and brain up to 120 min postoperatively, which was especially pronounced under the condition of PLR surgery.

Cited by 8 publications

References 41 publications

Surgery, neuroinflammation and cognitive impairment

Surgery, neuroinflammation and cognitive impairment

Neuroprotectin D1 Protects Against Postoperative Delirium-Like Behavior in Aged Mice

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

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