Circulating TNF-α levels increased and correlated negatively with IGF-I in postoperative cognitive dysfunction

Purpose: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. Methods: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor necrosis factor-α (TNF-α) were measured. The expression of macrophage phenotype was observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of FoxO1 and p21 were analyzed by immunoblotting (Western blot). Results: Compared with the control group, the freezing time in the anesthesia group was lower than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease of cognitive ability. The blood concentrations of CD163 and TNF-α increased significantly at 24 h after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1 phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high level of M1 mRNA, and the expression levels of TNF-α, monocyte chemotactic protein 1(MCP-1) and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-β (TGF-β) and IL-10 were significantly lower than those in the control group (P<0.05). Compared with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly lower than that in the control group with a significant statistical difference (P<0.01). Conclusion: This study offers a theoretical basis and insight for further understanding of the prevention and treatment of cognitive dysfunction induced by anesthetic drugs.

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Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

10.21203/rs.2.12725/v3 ◽

2019 ◽

Author(s):

Bi Xing-hua ◽

Zhou Long-yuan ◽

Cai Chang ◽

Qi Yong ◽

Yan Li

Keyword(s):

Learning And Memory ◽

Cognitive Dysfunction ◽

Cystatin C ◽

Postoperative Cognitive Dysfunction ◽

The Other ◽

Inflammatory Factors ◽

Aged Rats ◽

Tnf Α ◽

Neuro Inflammation ◽

Related Proteins

Abstract B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation.

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Electroacupuncture for the Prevention of Postoperative Cognitive Dysfunction Among Older Adults Undergoing Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Medicine ◽

10.3389/fmed.2021.778474 ◽

2022 ◽

Vol 8 ◽

Author(s):

Liang Ou ◽

Zhen Shen ◽

Tiantian Zhang ◽

Zehua Chen ◽

Lin Zhang ◽

...

Keyword(s):

Systematic Review ◽

Randomized Controlled Trials ◽

Cognitive Dysfunction ◽

Knee Replacement ◽

Meta Analysis ◽

Postoperative Cognitive Dysfunction ◽

Control Group ◽

Controlled Trials ◽

Randomized Controlled ◽

Tnf Α

Background: Postoperative cognitive dysfunction (POCD) is a common surgical complication in elderly patients undergoing hip and knee replacement. Electroacupuncture (EA) may have a protective effect on postoperative cognitive function, but relevant evidence remains uncertain.Objective: To systematically evaluate the evidence of EA for the prevention of POCD after total joint arthroplasty.Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and Chinese Biomedical Literature Database (CBM) databases were searched until May 1, 2021. Randomized controlled trials (RCTs) in which patients undergoing hip and knee replacement pretreated with EA for preventing POCD were included. The risk of bias was assessed by the Cochrane Collaboration tool. Meta-analysis was performed using Review Manager version 5.4.Results: A total of 11 RCTs with 949 patients were identified. Meta-analysis showed that compared with controls, EA pretreatment significantly reduced the incidence of POCD at 1, 3, and 7 days and 3 and 6 months after the operation. EA was also superior in improving the Mini-Mental State Examination (MMSE) scores on the third postoperative day, but not on the first postoperative day. Neuron-specific enolase (NSE) and interleukin-1β (IL-1β) in the EA group were significantly lower than that in the control group. There was no difference in S100β between the EA group and the control group. Compared to the control group, tumor necrosis factor-α (TNF-α) levels were not significantly lower in the EA group at postoperative hour 0, while significantly decreased at postoperative hours 24 and 48.Conclusion: Our results suggest that EA pretreatment is an effective adjunctive therapy for reducing the incidence of POCD for patients receiving total joint replacement surgery. Its effect was embodied in improving the MMSE scores and NSE, IL-1β, and TNF-α levels, whereas it had no significant effect on S100β levels. Meanwhile, the benefits of EA for improving POCD need further strengthening and support from more large-scale, high-quality, and good-homogeneity RCTs.Systematic Review Registration:https://osf.io/xb3e8.

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Preoperative smoking history is associated with decreased risk of early postoperative cognitive dysfunction in patients of advanced age after noncardiac surgery: a prospective observational cohort study

Journal of International Medical Research ◽

10.1177/0300060518808162 ◽

2018 ◽

Vol 47 (2) ◽

pp. 689-701 ◽

Cited By ~ 3

Author(s):

Runjia Wang ◽

Gongming Wang ◽

Yang Liu ◽

Mengyuan Zhang

Keyword(s):

Cognitive Dysfunction ◽

Postoperative Cognitive Dysfunction ◽

Noncardiac Surgery ◽

High Serum ◽

Advanced Age ◽

Smoking History ◽

Inflammatory Pathway ◽

Increased Risk ◽

Tnf Α ◽

Α Level

Objective Prevention of postoperative cognitive dysfunction (POCD) in patients of advanced age remains unclear. Studies have shown that the cholinergic anti-inflammatory pathway contributes to a decreased risk of POCD and that nicotine stimulates the cholinergic anti-inflammatory pathway. We investigated whether patients of advanced age with a preoperative smoking history have a decreased risk of POCD. Methods In total, 382 patients (190 smokers, 192 nonsmokers) aged ≥60 years who underwent major noncardiac surgery were enrolled. Cognitive function was assessed, and multivariate logistic regression analyses were performed to identify risk factors. Results On postoperative days 5 and 7, 111 (29.05%) and 90 (23.56%) patients exhibited POCD, respectively. A preoperative smoking history was significantly correlated with a decreased risk of POCD. A high serum tumor necrosis factor-α (TNF-α) level on the operative day was significantly associated with an increased risk of POCD. Early POCD was significantly associated with the sufentanil dosage, age, and education level. The hospital stay in patients with and without POCD was 10.54 ± 2.03 and 8.33 ± 1.58 days, respectively. Conclusion A preoperative smoking history was associated with a decreased risk of early POCD, and a high serum TNF-α level was significantly associated with an increased risk of POCD.

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Effect of Ulinastatin on Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Surgery: A Systemic Review and Meta-Analysis

Frontiers in Neuroscience ◽

10.3389/fnins.2021.618589 ◽

2021 ◽

Vol 15 ◽

Author(s):

Mei Duan ◽

Fangyan Liu ◽

Huiqun Fu ◽

Shuai Feng ◽

Xue Wang ◽

...

Keyword(s):

Elderly Patients ◽

Cognitive Dysfunction ◽

Inflammatory Responses ◽

Meta Analysis ◽

Postoperative Cognitive Dysfunction ◽

Systemic Review ◽

Cochrane Library ◽

Secondary Outcome ◽

Major Surgery ◽

Tnf Α

Background: Postoperative cognitive dysfunction (POCD) is associated with neuroinflammation by triggering the systemic inflammatory responses. Related studies have demonstrated that ulinastatin, which is a urinary trypsin inhibitor, inhibited the release of inflammatory mediators and improved postoperative cognitive function in elderly patients undergoing major surgery. However, there are controversial results put forwarded by some studies. This systemic review aimed to evaluate the effect of ulinastatin on POCD in elderly patients undergoing surgery.Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and Ovid to find relevant randomized controlled trials (RCTs) of ulinastatin on POCD in elderly patients undergoing surgery. The primary outcomes included the incidence of POCD and the Mini-Mental State Examination (MMSE) scores. The secondary outcome was the levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, S100β, C-reactive protein (CRP), interleukin (IL)-6, and IL-10. RevMan 5.3 was used to conduct the meta-analysis.Results: Ten RCTs were included finally. Compared with controls, ulinastatin significantly reduced the incidence of POCD [risk ratio (RR) = 0.29, 95% CI 0.21–0.41, test of RR = 1: Z = 7.05, p < 0.00001]. In addition, patients in the ulinastatin group have lower levels of TNF-α, S100β, CRP, and IL-6 and higher level of IL-10 in serum following surgery.Conclusion: These findings suggested that ulinastatin can be used as an anti-inflammatory drug for POCD prevention in elderly patients undergoing surgery.Systematic Review Registration Number: CRD42019137449.

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Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

10.21203/rs.2.12725/v1 ◽

2019 ◽

Author(s):

Bi Xing-hua ◽

Zhou Long-yuan ◽

Cai Chang ◽

Qi Yong ◽

Yan Li

Keyword(s):

Learning And Memory ◽

Cognitive Dysfunction ◽

Cystatin C ◽

Postoperative Cognitive Dysfunction ◽

The Other ◽

Aged Rats ◽

Chain Reaction ◽

Tnf Α ◽

Polymerase Chain ◽

Related Proteins

Abstract Background: This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C in aged rats undergoing splenectomy. Methods: Rats were randomized into four groups (n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Learning and memory were assessed postoperatively using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory cytokines IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion: Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuroinflammation.

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Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

10.21203/rs.2.12725/v2 ◽

2019 ◽

Author(s):

Bi Xing-hua ◽

Zhou Long-yuan ◽

Cai Chang ◽

Qi Yong ◽

Yan Li

Keyword(s):

Learning And Memory ◽

Cognitive Dysfunction ◽

Cystatin C ◽

Postoperative Cognitive Dysfunction ◽

The Other ◽

Inflammatory Factors ◽

Aged Rats ◽

Tnf Α ◽

Neuro Inflammation ◽

Related Proteins

Abstract B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation.

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Postoperative Cognitive Dysfunction In Older Alcoholics

PsycEXTRA Dataset ◽

10.1037/e643742007-001 ◽

2007 ◽

Author(s):

Judith A. Hudetz ◽

Diane Reddy ◽

Kathleen Patterson ◽

Anthony G. Hudetz ◽

David C. Warltier

Keyword(s):

Cognitive Dysfunction ◽

Postoperative Cognitive Dysfunction

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Postoperative cognitive dysfunction: progress mechanisms and clinical characteristics

Medical alphabet ◽

10.33667/2078-5631-2019-2-19(394)-29-33 ◽

2019 ◽

Vol 2 (19) ◽

pp. 29-33

Author(s):

K. B. Manysheva ◽

M. A. Akhmedov ◽

A. A. Rakhmanova ◽

S. M. Khutalieva

Keyword(s):

Cognitive Dysfunction ◽

Clinical Characteristics ◽

Cognitive Deficit ◽

Neuropsychological Testing ◽

Postoperative Cognitive Dysfunction ◽

Clinical Manifestations ◽

Postoperative Recovery ◽

Neuropsychological Rehabilitation ◽

Brain Barrier Permeability ◽

The Central Nervous System

The article is devoted to the study of postoperative cognitive dysfunction — a syndrome that is often found in the postoperative period and does not depend on the volume of surgeon. Based on the analysis of the results of modern studies, the authors cite the most likely etiological causes of the syndrome, grouped according to different categories of risk factors. The pathogenetic algorithm for cognitive dysfunction includes the appearance of systemic inflammation, improving blood-brain barrier permeability with the endothelial dysfunction, the migration of inflammatory agents into the central nervous system, and the formation of oxidative stress. The clinical manifestations of cognitive deficit in the outcome of surgeon performed under general anesthesia, the authors illustrate with their own observations of patients with a neurosurgical profile with spinal pathology operated on with the use of propofol anesthesia, comparing the results of neuropsychological testing with an assessment of the level of anxiety. In conclusion, the authors outline a strategy for the prevention of postoperative cognitive dysfunction and recommend conducting neuropsychological rehabilitation as an important component of postoperative recovery for all patients with a diagnosed cognitive deficit that occurred after surgery.

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