NLRP3 inflammasomes are involved in the progression of postoperative cognitive dysfunction: from mechanism to treatment

Zhao, Shuai; Chen, Fan; Wang, Dunwei; Han, Wei; Zhang, Yuan; Yin, Qiliang

doi:10.1007/s10143-020-01387-z

Cited by 22 publications

(18 citation statements)

References 178 publications

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“…The persistent and excessive inflammation is crucial in the pathophysiologic mechanism of sevoflurane aesthesia-induced neurological dysfunction [24]. The sevoflurane-induced neuroinflammation can be ameliorated by repressing the activation of NLRP3, which is related to the sevoflurane-triggered pathological damage [25]. In this study, compared with C group, the expressions of NLRP3, GSDMD and Caspase-1 presented the consistent variation trends with the expressions of TRIF, p-RIP3 and CaMKII in the hippocampal tissues and neurons of neonatal mice in SEV group.…”

Section: Discussionmentioning

confidence: 99%

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction

Zhang

et al. 2022

Aging

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This research aimed to explore the influence of TLR deletion on sevoflurane-induced postoperative cognitive dysfunction in neonatal mice. Herein, WT and TLR3 KO neonatal mice, each with 24, were randomly divided into control group, sevoflurane group, and TLR3 −/− +sevoflurane group. The hippocampal neurons of WT, TLR3 KO and RIP3 KO neonatal mice in C group, SEV group, TLR3 −/− +SEV group and RIP3 −/− +SEV group were extracted for in vitro experiments. The results revealed the degeneration and necrosis of nerve cells in SEV group. Microscopic findings indicated that nerve cells showed shrinkage and nuclear hyperchromatism, along with lessening or even disappearance of nuclei and enlargement of cell spaces, and apoptotic cells in the brain tissues were evidently increased. Compared with SEV group, TLR3 −/− +SEV group displayed reductions in these phenomena. Additionally, SEV group showed the reduced SHP2 expression and the increased expressions of proteins associated with TLR signaling pathway and apoptosis. Furthermore, there were no obvious differences in the expressions of such proteins in hippocampal neurons between RIP3 −/− +SEV and TLR3 −/− +SEV groups. The results confirmed that inhibiting RIP3 phosphorylation and suppressing TLR3 expressions exerted the same influence on the expressions of these proteins in the hippocampus of neonatal mice with sevoflurane-induced cognitive dysfunction. Based on these, it is speculated that TLR3 influences neonatal mice with sevofluraneinduced cognitive dysfunction probably by regulating RIP3 phosphorylation.

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Section: Discussionmentioning

confidence: 99%

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction

Zhang

et al. 2022

Aging

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“…In severe COVID‐19 cases, the serum levels of IL‐2, IL‐1β, IL‐6, IFN‐γ, MIP1A, MCP‐1, and TNF‐α are increased 63,64 . After SARS‐Cov‐2 infection, it can trigger the activation of the NOD‐like receptor protein 3 (NLRP3) inflammasome and the secretion of IL‐1b in bone marrow‐derived macrophages, 52,65,66 which can induce apoptosis and cause the release of inflammatory mediators 65 . Endothelial cell activation is an important part of systemic inflammation and immune response, TNFα can induce the activation of SphK1 and S1P in cells, thereby mediating the activation of endothelial cells and the expression of adhesion molecules 67 .…”

Section: Pathogenic Mechanisms Of Sars‐cov‐2 and Potential Role Of The Sphk‐s1p‐sipr Pathwaymentioning

confidence: 99%

Role of the SphK‐S1P‐S1PRs pathway in invasion of the nervous system by SARS‐CoV‐2 infection

Pan

Gao

Zhao

et al. 2021

Clin Exp Pharma Physio

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Global spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is still ongoing. Before an effective vaccine is available, the development of potential treatments for resultant coronavirus disease 2019 (COVID‐19) is crucial. One of the disease hallmarks is hyper‐inflammatory responses, which usually leads to a severe lung disease. Patients with COVID‐19 also frequently suffer from neurological symptoms such as acute diffuse encephalomyelitis, brain injury and psychiatric complications. The metabolic pathway of sphingosine‐1‐phosphate (S1P) is a dynamic regulator of various cell types and disease processes, including the nervous system. It has been demonstrated that S1P and its metabolic enzymes, regulating neuroinflammation and neurogenesis, exhibit important functions during viral infection. S1P receptor 1 (S1PR1) analogues including AAL‐R and RP‐002 inhibit pathophysiological responses at the early stage of H1N1 virus infection and then play a protective role. Fingolimod (FTY720) is an S1P receptor modulator and is being tested for treating COVID‐19. Our review provides an overview of SARS‐CoV‐2 infection and critical role of the SphK‐S1P‐SIPR pathway in invasion of SARS‐CoV‐2 infection, particularly in the central nervous system (CNS). This may help design therapeutic strategies based on the S1P‐mediated signal transduction, and the adjuvant therapeutic effects of S1P analogues to limit or prevent the interaction between the host and SARS‐CoV‐2, block the spread of the SARS‐CoV‐2, and consequently treat related complications in the CNS.

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“…Aberrant activation of NLRP3 inflammasome is involved in inflammatory diseases, Alzheimer's disease, diabetes and cancers (Huang et al, 2021). Overactivation of NLRP3 inflammasome contributes to the progression of POCD (Zhao et al, 2021). NLRP3 inflammasome regulates the activation of caspase-1 and mediates the maturation and secretion of IL-1β and IL-18, thus associating with neuroinflammation and oxidative stress during progression of POCD (Wei et al, 2019).…”

Section: Ruscogenin Suppressed Nlrp3 Pathwaymentioning

confidence: 99%

Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

Xiao-hu

Luo

et al. 2021

qas

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Ruscogenin exerts an anti-inflammatory effect in the pathogenesis of various human diseases, including pulmonary hypertension, acute lung injury, acute pancreatitis and cerebral ischemia. Its role in isoflurane-induced rats with postoperative cognitive dysfunction (POCD) was investigated in this study. Aged rats were exposed to isoflurane for establishing a model of POCD, and administered with ruscogenin by gavage. Cognitive dysfunction was evaluated by the Morris water maze test. Hematoxylin and Eosin (H&E) staining was designed to assess neuronal damage. Markers of brain damage and neuroinflammation were detected by enzyme-linked-immunosorbent serologic assay. Isoflurane exposure caused impaired cognitive function by increasing escape latency, decreasing the time taken for crossing target and time in target quadrant. However, administration of ruscogenin reversed these cognitive dysfunctions. Abnormal morphological phenomena on neurons and enhanced levels of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) were identified in mice post-isoflurane exposure. Administration of ruscogenin ameliorated the neuronal morphological damages and reduced the levels of S-100β and NSE in the hippocampi of isoflurane-induced aged mice. Ruscogenin also attenuated isoflurane-induced enhancements in the levels of Interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha in the hippocampi of mice. Isoflurane-induced enhancements in the mRNA expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, IL-1β and IL-18 proteins were also restored by administration of ruscogenin. Ruscogenin exerted neuroprotective effects against isoflurane-induced cognitive dysfunction and neuroinflammation through blocking of NLRP3 pathway.

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NLRP3 inflammasomes are involved in the progression of postoperative cognitive dysfunction: from mechanism to treatment

Cited by 22 publications

References 178 publications

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction

Role of the SphK‐S1P‐S1PRs pathway in invasion of the nervous system by SARS‐CoV‐2 infection

Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

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