The potential mechanism of postoperative cognitive dysfunction in older people

Lin, Xiao; Chen, Yeru; Zhang, Haining; Chen, Gang; Zhou, Youfa; Yu, Xiao-Chun

doi:10.1016/j.exger.2019.110791

Cited by 189 publications

(169 citation statements)

References 179 publications

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“…Post-operative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive impairments in patients after anaesthesia and surgery, 1 and its pathogenesis and pathophysiology remain inconclusive. In the past decade although multiple hypotheses, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, blood-brain barrier (BBB) impairment, synaptic dysfunction, lacking neurotrophic support and cholinergic failure, 2 have been raised, neuroinflammation is believed to play an initial and central role in the development of POCD. [3][4][5] During perioperative periods, pro-inflammatory cytokines, such as tumour necrosis factor-α (TNF-α) and interleukin I, were released from activated macrophages and monocytes.…”

Section: Introductionmentioning

confidence: 99%

Calpain‐2 plays a pivotal role in the inhibitory effects of propofol against TNF‐α‐induced autophagy in mouse hippocampal neurons

Liu

et al. 2020

J Cellular Molecular Medi

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Calpains are calcium‐dependent proteases and play critical roles in neuronal autophagy induced by inflammation. Propofol has been reported to exert anti‐inflammatory effects in neurons. We aimed to identify whether and how propofol‐modulated calpain activity and neuron autophagy in response to tumour necrosis factor‐α (TNF‐α). Mouse hippocampal neurons were pre‐treated with propofol and exposed to TNF‐α. Autophagy was evaluated by fluorescent autophagy assay and by measuring LC3I and LC3II expression. Intracellular calcium concentration was measured by fluorescent assay. Calpain activation was measured by calpain activity assay. The protein expression of intracellular signalling molecules was detected by Western blot analysis. Compared with untreated control neurons, 40 ng/mL TNF‐α treatment for 2 hours induced neuron autophagy, which was attenuated by 25 μmol/L propofol. TNF‐α induced intracellular calcium accumulation, the phosphorylation of calcium/calmodulin‐dependent protein kinase II (CAMK II) and calpain‐2, calpain activation and lysosomal cathepsin B release as well as tyrosine kinase receptor B (TrkB) truncation. These effects were alleviated by propofol, calcium chelator, CAMK II inhibitor, calpain‐2 inhibitor, calpain‐2 siRNA transfection and N‐Methyl‐ d ‐aspartic acid (NMDA) receptor antagonist. Propofol, via NMDA receptor, inhibited TNF‐α‐mediated hippocampal neuron autophagy. The mechanism may involve calcium and calcium‐dependent signalling pathway, especially CAMK II and calpain‐2.

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Section: Introductionmentioning

confidence: 99%

Calpain‐2 plays a pivotal role in the inhibitory effects of propofol against TNF‐α‐induced autophagy in mouse hippocampal neurons

Liu

et al. 2020

J Cellular Molecular Medi

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“…POCD pathogenesis has not been properly clarified, but it is affirmatory that POCD is a complication of cardinal surgery induced by multiple factors. Some recognized important risk factors of POCD include the advanced age, combined metabolic diseases, operative procedure, anesthesia induction, pre-existing cerebrovascular and systemic vascular diseases, and systemic inflammation [4]. However, the risk factors vary among different studies because of the variant diagnosis of POCD, diverse analysis procedures, and subjective effects [5].…”

Section: Introductionmentioning

confidence: 99%

Preoperative red cell distribution width predicts postoperative cognitive dysfunction after coronary artery bypass grafting

Wan

Luo

et al. 2020

Bioscience Reports

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We assessed the relationship between red blodd cell distribution width (RDW) and postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG) in patients who usually had obvious hemodynamic changes. We enrolled 362 coronary heart disease patients who received CABG. POCD was assessed through neuropsychological examination at 21 days after operation. Demographics, history of diseases, blood biochemical parameters and perioperative data were collected. The receiver operating characteristic (ROC) curve was used to find the best cut-off value of RDW for diagnosis of POCD. Logistic regression was used to explore the relationship between RDW and POCD. The 21-day incidence of POCD in patients receiving CABG was 27.1% (98/362). The RDW of POCD patients was significantly higher than in the non-POCD patients (17.4 vs. 13.2). The sensitivity and specificity of RDW for predicting POCD were 82.7 and 64.8%, respectively. The POCD patients also tended to be older and had higher fasting plasma glucose, hypersensitive c-reactive protein, tumor necrosis factor-α, white blood cell levels and longer surgery time. No significant differences were found in other parameters. The 21-day neuropsychological test results were better in the POCD patients than the non-POCD patients. After adjustment of potential factors, the preoperative high RDW was still associated with an increased risk of POCD (odds ratio (OR) = 2.52, 95% confidence interval (CI): 1.28–4.31). Our study indicates that preoperative RDW is significantly elevated in POCD patients receiving CABG. The elevated preoperative RDW is associated with an increased risk of POCD and preoperative RDW can be an independent predictor of POCD.

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“…Similarly, in this study, postoperative IL-6 increase was also influenced by age. Age (> 60 years old) has been suggested to be a risk factor for the development of PND [5,17]; several studies confirm this association [24,25].…”

Section: Constitutional Risk Factors: Inflammagingmentioning

confidence: 99%

Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study

Saxena¹,

Rodts

Nuyens

et al. 2020

BMC Anesthesiol

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Background Surgical interventions result in a postoperative rise in circulating inflammatory cytokines and high molecular group box protein 1 (HMGB1). Herein, the impact of a sedentary lifestyle and other age-related factors on the development of perioperative neurocognitive disorders (PND) following non-cardiac surgical procedures was assessed in an older (55–75 years-old) surgical population. Methods Prior to surgery, patients were asked questions regarding their sedentary behavior and daily habits. They also passed the Mini Mental State Examination (MMSE) and their blood circulating interleukin 6 (IL-6) and HMGB1 levels were assayed by ELISA. IL-6 and HMGB1 measurements were repeated respectively 6 and 24 h after surgery. MMSE was re-evaluated 6 weeks and whenever possible 3 months after surgery. Results Thirty-eight patients were enrolled in the study from January until July 2019. The study identified self-sufficiency, multilinguism, and overall health score on the geriatric depression scale, as protectors against PND. No other demographic (age, sex), environmental (solitary/non-solitary housing, professional and physical activities, smoking, alcohol drinking), comorbidity (antipsychotic drug uptake, diabetic state) and type of surgery (orthopedic, general, genitourinary) influenced the development of PND. Although some factors (surgery type and age) influenced the surgery-induced rise in the circulating IL-6 levels, they did not impact HMGB1. Conclusion Inflammaging, reflected by the greater increment of surgery-induced IL-6 in patients with advanced age, was present. As trauma-induced release of HMGB1 was not similarly affected by age, we surmise that HMGB1, rather than circulating cytokines, is the key driver of the trauma-induced inflammatory cascade leading to PND. Trial registration Clinicaltrials.gov identifier: NCT03805685.

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The potential mechanism of postoperative cognitive dysfunction in older people

Cited by 189 publications

References 179 publications

Calpain‐2 plays a pivotal role in the inhibitory effects of propofol against TNF‐α‐induced autophagy in mouse hippocampal neurons

Calpain‐2 plays a pivotal role in the inhibitory effects of propofol against TNF‐α‐induced autophagy in mouse hippocampal neurons

Preoperative red cell distribution width predicts postoperative cognitive dysfunction after coronary artery bypass grafting

Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study

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