Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption

Zhang, Susu; Dong, Huijuan; Zhang, Xiang; Li, Nana; Sun, Jie; Qian, Yanning

doi:10.1016/j.bbr.2015.11.003

Cited by 73 publications

(62 citation statements)

References 40 publications

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“…We previously demonstrated that MC degranulation can disrupt the BBB [4]. We also found that the supernatant from activated MCs can induce mouse brain microvascular endothelial cell activation and promote the secretion of the inflammatory cytokines TNF-α and IL-6.…”

Section: Introductionmentioning

confidence: 94%

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Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2

Zhou

Wang

et al. 2018

J Neuroinflammation

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BackgroundMast cells (MCs), the ‘first responders’ in brain injury, are able to disrupt the blood–brain barrier (BBB), but the underlying mechanism is not well understood. Tryptase is the most abundant MC secretory product. Protease-activated receptor 2 (PAR-2) has been identified as a specific receptor for tryptase, which is abundantly expressed in brain microvascular endothelial cells. The BBB comprises brain microvascular endothelial cells that display specialised molecular properties essential for BBB function and integrity. Therefore, the purpose of the present study was to investigate the effects of tryptase on mouse brain microvascular endothelial cell line bEnd3 and its potential mechanisms of action.MethodsInduction of mouse brain microvascular endothelial cell activation by tryptase was examined. Then, mouse brain microvascular endothelial cells were pretreated with a PAR-2 antagonist and stimulated with tryptase. Cellular activation, proinflammatory cytokine production, expression of PAR-2, Toll-like receptors (TLRs) and mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-kappa B) phosphorylation were assessed.ResultsTryptase upregulated the production of VCAM-1, MMPs (MMP9 and MMP2), TLR4 and TNF-α and downregulated the expression of the tight junction proteins occludin and claudin-5 in mouse brain microvascular endothelial cell. Among the MAPK and NF-kappa B pathway, ERK and NF-kappa B were activated by tryptase. All of these effects could be eliminated by the PAR-2 inhibitor.ConclusionBased on our findings, we conclude that tryptase can trigger brain microvascular endothelial cell activation and proinflammatory mediator release. These findings may further clarify the involvement and mechanism of tryptase in BBB disruption.

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Section: Introductionmentioning

confidence: 94%

“…There is increasing evidence showing that MC degranulation in the brain is involved in central nervous system (CNS) inflammatory processes [2–4]. However, the mechanisms underlying how mast cells disrupt the BBB are unclear.…”

Section: Introductionmentioning

confidence: 99%

Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2

Zhou

Wang

et al. 2018

J Neuroinflammation

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“…[30–32] Inflammatory factors that are induced in patients who have undergone surgical procedures penetrate the blood–brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation and influence inflammatory processes in the central nervous system. [33,34] In particular, the normal ageing brain is susceptible to neuroinflammation, and activation of the peripheral innate immune system can induce an amplified and prolonged inflammatory response in the brain.…”

Section: Discussionmentioning

confidence: 99%

Remote ischemic preconditioning improves the cognitive function of elderly patients following colon surgery

2017

Medicine

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Background:Cognitive function impairment is one of the most common complications in elderly patients after surgery, and an ideal nonpharmacological therapy has not yet been identified. Thus, we hypothesized that remote ischemic preconditioning could improve cognitive functions in elderly patients after surgery and investigated the mechanism underlying this effect.Methods:Ninety patients classified as American Society of Anaesthesiologists (ASA) physical status of 2 or 3 and aged 65 to 75 years who were scheduled for elective colon surgery under general anesthesia were randomly allocated to either a remote ischemic preconditioning group (Group R, n = 45) or a control group (Group C, n = 45). Remote ischemic preconditioning was performed by applying a static pressure of 200 mm Hg with a blood pressure cuff wrapped around the right upper limb for 3 ischemia cycles of 5 minutes each.Results:The Montreal Cognitive Assessment (MoCA) scores between the 2 groups were not significantly different on the day before surgery or the seventh day after surgery, but the scores on the first day after surgery (26.87 ± 0.84 vs 25.96 ± 0.85, P < .001) and third day after surgery (27.49 ± 0.66 vs 27.02 ± 0.92, P = .009) were significantly higher for Group R than those for Group C. Moreover, remote ischemic preconditioning markedly decreased the serum concentrations of the interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and S100B proteins compared with the control group (P < .001).Conclusion:Remote ischemic preconditioning improves postoperative cognitive function in elderly patients following colon surgery. The cognitive protective effects of remote ischemic preconditioning are partially related to the inhibition of inflammation.

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“…Surgery can lead to blood-brain barrier dysfunction and induce systemic inflammatory response (12,26). There is a detailed review of this mechanism described by Vacas et al (27).…”

Section: Mechanismsmentioning

confidence: 99%

“…The possible mechanisms of POCD investigated included platelet activation (17), oxidative stress (18), cholinergic function impairment (19,20), impairment of synaptic integrity (2,21), similar mechanisms of Alzheimer's disease (AD) such as beta-amyloid accumulation (22,23) and tau phosphorylation (24), and immune response and inflammation related mechanisms such as the bone marrow-derived macrophages recruitment in hippocampal area (25) and the recent popular surgery-induced neuroinflammation (12,26,27) (Table 2).…”

Section: Mechanismsmentioning

confidence: 99%

Difficulties in Understanding Postoperative Cognitive Dysfunction

An¹,

Yu²

2017

J Anesth Perioper Med

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Aim of review:Firstly brought up by Bedford in 1955, postoperative cognitive dysfunction (POCD) has been given increasing attention due to the increase of the elderly population. Although many researches have been conducted on POCD, the understanding of this clinical syndrome is still limited. There are currently many disputes regarding almost every aspects of POCD, even the term itself has not been included in the MeSH Database. This review aims to discuss the major disputes about POCD that hinder research consistency and provide possible perspectives for future research. Method: Recent articles and literatures about POCD were searched and reviewed. First, basic knowledge of POCD, including characteristics and incidence, risk factors, mechanisms, prevention and intervention are introduced. Second, the major obstacles of investigating POCD are discussed. Then two major problems are proposed: 1) Does the POCD in patients really start postoperatively? 2) Is POCD only related to old age? Finally, the never-ending argument regarding the role of anesthesia on POCD is discussed. Recent findings: Recent researches regarding POCD focused on the surgery-related neuroinflammation mechanism, and efforts have been made to find some biomarkers of POCD. In terms of POCD, there are many fundamental concepts and in urgent need of consensus. First, unifying the terms used among studies will benefit the communication of knowledge. Second, questions like whether POCD should be defined as a general cognitive decline that include other forms such as postoperative delirium, or they should be considered as separate unique illnesses, and whether or not young patients should be included when POCD is discussed, need to be answered. Only after answering these questions, will the study of POCD be less disputable. Third but not the least, efforts should be made trying to make "golden-standard" in regard of the testing methods of POCD both clinically and pre-clinically. Summary: Although lots of researches have been conducted on POCD, the understanding of this clinical syndrome is still very limited. There are currently many disputes regarding almost every aspect of POCD. It's time for clinicians and scholars to strike some fundamental consensus for the better investigation of POCD. How to find a way to increase the rigor of experimental design is an important question that still seeks answers.

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Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption

Cited by 73 publications

References 40 publications

Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2

Effect of tryptase on mouse brain microvascular endothelial cells via protease-activated receptor 2

Remote ischemic preconditioning improves the cognitive function of elderly patients following colon surgery

Difficulties in Understanding Postoperative Cognitive Dysfunction

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