Postoperative cognitive dysfunction in the aged: the collision of neuroinflammaging with perioperative neuroinflammation

Luo, Ailin; Yan, Jing; Tang, Xiaole; Zhao, Yilin; Zhou, Bing; Li, Shiyong

doi:10.1007/s10787-018-00559-0

Cited by 90 publications

(63 citation statements)

References 143 publications

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“…Neuroinflammation has been considered as a major pathogenesis of POCD, through exerting noxious effects on neurons, synapsis and BBB. [3][4][5] Previous studies have revealed that pro-inflammatory cytokine TNF-α may induce dopaminergic neuron apoptosis, deteriorate brain microglia and astrocyte function, modulate synaptic plasticity and impair neuronal tight junction as well BBB integrity. [9][10][11][12][13]30 Hippocampal neurons play important roles in learning and memory, and excessive hippocampal neuron autophagy was revealed to be extensively involved in the development of POCD.…”

Section: The Effect Of Tnf-α On Hippocampal Neuron Autophagymentioning

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: The Effect Of Tnf-α On Hippocampal Neuron Autophagymentioning

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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“…Enhanced inflammation response has been increasingly reported in association with POCD [161]. Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation.…”

Section: Postoperative Cognitive Dysfunctionmentioning

confidence: 99%

Anesthetic management of geriatric patients

Lim

2020

Korean J Anesthesiol

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The number of elderly patients who frequently access health care services is increasing worldwide. While anesthesiologists are developing the expertise to care for these elderly patients, areas of concern remain. We conducted a comprehensive search of major international databases (PubMed, Embase, and Cochrane) and a Korean database (KoreaMed) to review preoperative considerations, intraoperative management, and postoperative problems when anesthetizing elderly patients. Preoperative preparation of elderly patients included functional assessment to identify preexisting cognitive impairment or cardiopulmonary reserve, depression, frailty, nutrition, polypharmacy, and anticoagulation issues. Intraoperative management included anesthetic mode and pharmacology, monitoring, intravenous fluid or transfusion management, lung-protective ventilation, and prevention of hypothermia. Postoperative checklists included perioperative analgesia, postoperative delirium and cognitive dysfunction, and other complications. A higher level of perioperative care was required for older surgical patients, as multiple chronic diseases often makes them prone to developing postoperative complications, including functional decline and loss of independence. Although the guiding evidence remains poor so far, elderly patients have to be provided optimal perioperative care through close interdisciplinary, interprofessional, and cross-sectional collaboration to minimize unwanted postoperative outcomes. Furthermore, along with adequate anesthetic care, well-planned postoperative care should begin immediately after surgery and extend until discharge.

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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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Postoperative cognitive dysfunction in the aged: the collision of neuroinflammaging with perioperative neuroinflammation

Cited by 90 publications

References 143 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

Anesthetic management of geriatric patients

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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