The Role of Microglia in Perioperative Neurocognitive Disorders

Fan, Wenguo; Mai, Lijia; Zhu, Xiao; Huang, Fang; He, Hongwen

doi:10.3389/fncel.2020.00261

Cited by 25 publications

(16 citation statements)

References 112 publications

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“…Inflammation associated with POCD involves both central and peripheral compartments 5,6 . Surgery activates an immune response and results in the release of systemic proinflammatory factors and eventually leads to neuroinflammation 7–9 . Studies have shown that microglia are activated by peripheral proinflammatory cytokines 10 and can release additional proinflammatory cytokines, exacerbating neuroinflammation and brain damage 11 .…”

Section: Introductionmentioning

confidence: 99%

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Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

et al. 2021

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Background Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA’s regulatory role of inflammasomes remain unclear. Methods The model of POCD was established by partial hepatectomy surgery in 18‐month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL‐1β and IL‐6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF‐κB pathway proteins were evaluated by western blotting. Results EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL‐1β and IL‐6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO‐1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF‐κB was inhibited by EA, while NLRP3 activation abolished EA’s treatment effects on cognitive function. Conclusion EA alleviates POCD‐mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA’s treatment effects are dependent on NLRP3 inhibition.

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Section: Introductionmentioning

confidence: 99%

“…However, under pathological conditions, the hippocampus is particularly vulnerable to proinflammatory factors. Therefore, the release of proinflammatory cytokines by M1‐type microglia may lead to the injury of hippocampus and eventually lead to POCD 7 …”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

et al. 2021

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“…Especially, microglia are the main participants in the brain's immune response. Furthermore, microglia dysfunction that occurs after anesthesia and surgery may disrupt neuronal function and induce PND [23]. P2X4 is mainly expressed in microglia in the CNS, where this receptor is involved in various functions under physio-logical conditions [6,8].…”

Section: Discussionmentioning

confidence: 99%

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders

Yuan

et al. 2022

Mediators of Inflammation

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Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12–14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1β, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.

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“…The release of in ammatory cytokines causes neuronal damage and amplify the in ammatory response in CNS 30 . And then, we used two types of co-culture systems according to the ideas of our predecessors [31][32][33][34] , CM co-culture system and Transwell co-culture system, to verify the neuroprotective effects of PK11195 and Midazolam.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of TSPO ligands on neuronal damage mediated by LPS-stimulated BV-2 microglial activation

Liu

Zhang

et al. 2021

Preprint

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Background Neuroinflammation mediated by microglia is an important pathological process of neurodegenerative diseases. Alleviating the inflammatory response caused by activated microglia might be a valuable treatment. The 18-kDa translocator protein (TSPO), as a marker of neuroinflammation, is significantly elevated in activated microglia. But the function of TSPO in microglia has not been well demonstrated. Methods In this study, we evaluated the role of TSPO and its ligands in LPS-activated BV-2 microglia involving mitophagy pathway and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Then, in the microglia-neuron co-culture system, the neurotoxicity induced by LPS-activated microglia and the neuroprotective effects of TSPO ligands were evaluated. Results Our results showed that after stimulated by LPS, TSPO expression was increased, meanwhile the expression of autophagy associated proteins were decreased in BV-2 microglia cells, but the reduction was reversed by pretreatment with PK11195 and Midazolam. Simultaneously, the NLRP3 inflammasome were increased in LPS activated BV-2 microglia in Transwell co-culture system, pretreatment with TSPO ligands could curb this undesirable situation. Furthermore, TSPO ligands improved the cell viability and reduced apoptosis of neuronal cells in co-culture system. Conclusions TSPO ligands PK11195 and Midazolam showed neuroprotective effects by reducing the inflammatory response of LPS-activated microglia, which may be related to the enhancement of mitophagy and the inhibition of NLRP3 inflammasome.

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The Role of Microglia in Perioperative Neurocognitive Disorders

Cited by 25 publications

References 112 publications

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders

Efficacy of TSPO ligands on neuronal damage mediated by LPS-stimulated BV-2 microglial activation

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