Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment

Wang, Zhi; Meng, Shiyu; Cao, Lin; Chen, Ying; Zuo, Zhiyi; Peng, Shu-Ling

doi:10.1186/s12974-018-1137-1

Cited by 165 publications

(163 citation statements)

References 49 publications

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“…17 The contents of IL-1, IL-6, and TNF-α in the patientʼs plasma will be increased, which are closely related to the degree of surgical trauma. 19 Thus, they will activate the neuroglial cells, and produce a series of immune reactions to produce excessive inflammatory substances (IL-1β, IL-6, TNF-α, interferon-γ, cyclooxygenase-2, and complement) in the central nervous system. 18 In the case of a peripheral inflammatory response, a large number of inflammatory factors will enter the brain tissue through various pathways.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells regulate TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice

Sun

Li²,

et al. 2019

J of Cellular Biochemistry

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Background Postoperative cognitive dysfunction (POCD) is one of the common postoperative complications, which is more common in aged patients. POCD mainly manifests as cognitive function changes after surgery, such as memory decline and inattention. In some severe cases, patients may suffer from personality changes and (or) social behavior decline. The aim of the current study is to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in postoperative central inflammatory mice. Methods Mice were randomly assigned to four groups: sham, sham+BMSCs, model, and BMSCs group. In the model group, mice were intraperitoneally injected 8 mg/kg per day lipopolysaccharide for 5 days. In sham+BMSCs and BMSCs group, BMSCs (1 × 10 7) in 100 µL saline were injected into sham mice and model mice, respectively. Results In the model group, transforming growth factor β (TGF‐β) protein expression was significantly increased, compared with that in the sham group. BMSCs were treated into postoperative central inflammatory mice, which resulted in a decreased of TGF‐β protein expression. TGF‐β and smad2 protein expression were suppressed, and apoptosis rate and inflammation were inhibited in coculture with BMSCs. The suppression of TGF‐β inhibited the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. The promotion of TGF‐β reduced the effects of BMSCs on apoptosis rate and inflammation in postoperative central inflammatory through a smad2 signaling pathway. Conclusion The present study demonstrates that BMSCs regulates TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice.

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Section: Discussionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells regulate TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice

Sun

Li²,

et al. 2019

J of Cellular Biochemistry

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Section: Perioperative Neurocognitive Disordersmentioning

confidence: 99%

“…The inflammasome has been reported to be related to the pathogenesis of PND in various murine models [16,69,77,78]. In a mouse model subjected to anesthesia (isoflurane), aged mice, but not young ones, showed activation of the NLRP3-caspase-1 pathway, poor performance in the Morris water maze, and increased levels of IL-1β and IL-18 [16]. Moreover, in mice subjected to major abdominal surgery, components of the NLRP1 inflammasome complex are expressed and IL-1β and IL-18 are highly produced in the spleen, whereas the inhibition of the NF-κB p65 transcript reduced these effects [77].…”

Section: Perioperative Neurocognitive Disordersmentioning

confidence: 99%

“…Ac-YVAD-CMK, NF-κB p65 inhibition, and Honokiol contribute to reducing the inflammasome and ameliorating cognitive impairment in PND models [16,77,78]. Ac-YVAD-CMK can attenuate anesthesia (isoflurane)-induced activation of NLRP3 inflammasome in aged brain, thus ameliorating cognitive deficits [16].…”

Section: Perioperative Neurocognitive Disordersmentioning

confidence: 99%

“…However, it can drive human diseases, including inflammatory and neurodegenerative diseases. The association of the inflammasome with cognitive symptoms and inflammasome-associated pathophysiology have been reported in several pathological conditions [15][16][17][18][19]. Therefore, understanding the mechanisms regulating the inflammasome complex may be important for preventing or treating cognitive disorders.…”

Section: Introductionmentioning

confidence: 99%

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Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Cheon

Kim

et al. 2020

IJMS

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Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.

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Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice

Zhao

Deng

Shen³

et al. 2019

Ann Clin Transl Neurol

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Background Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19–52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood. Methods We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S‐adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested. Results PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S‐adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice. Conclusions Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.

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Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment

Cited by 165 publications

References 49 publications

Bone marrow mesenchymal stem cells regulate TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice

Bone marrow mesenchymal stem cells regulate TGF‐β to adjust neuroinflammation in postoperative central inflammatory mice

Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice

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