Comparison of metabolic rates of ropivacaine in cerebrospinal fluid as inferred from plasma concentrations between elderly patients and young patients.

BACKGROUND: With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. METHODS: Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18-30 years old and 75-90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aß protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. RESULTS: The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aß protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. CONCLUSIONS: This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people.

Early postoperative neurocognitive complications in elderly patients: comparing those with and without preexisting mild cognitive impairment- a prospective study.

BACKGROUND: As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. METHODS: A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72 h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. RESULTS: The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. CONCLUSIONS: The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. TRIAL REGISTRATION: This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Akkermansia muciniphila-derived small extracellular vesicles attenuate intestinal ischemia-reperfusion-induced postoperative cognitive dysfunction by suppressing microglia activation via the TLR2/4 signaling.

Akkermansia muciniphila (AKK) bacteria improve the functions of theere intestinal and blood-brain barriers (BBB) via their extracellular vesicles (AmEvs). However, their role in postoperative cognitive dysfunction (POCD) and its underlying mechanisms remain unclear. To investigate, we used C57BL/6 J mice divided into five groups: Sham, POCD, POCD+Akk, POCD+Evs, and POCD+Evs + PLX5622. POCD was induced through intestinal ischemia-reperfusion (I/R). The mice's cognitive function was assessed using behavioral tests, and possible mechanisms were explored by examining gut and BBB permeability, inflammation, and microglial function. Toll-like receptor (TLR) 2/4 pathway-related proteins were also investigated both in vitro and in vivo. PLX5622 chow was employed to eliminate microglial cells. Our findings revealed a negative correlation between AKK abundance and POCD symptoms. Supplementation with either AKK or AmEvs improved cognitive function, improved the performance of the intestinal barrier and BBB, and decreased inflammation and microglial activation in POCD mice compared to controls. Moreover, AmEvs treatment inhibited TLR2/4 signaling in the brains of POCD mice and LPS-treated microglial cells. In microglial-ablated POCD mice, however, AmEvs failed to protect BBB integrity. Overall, AmEvs is a potential therapeutic strategy for managing POCD by enhancing gut and BBB integrity and inhibiting microglial-mediated TLR2/4 signaling.

J147 affects cognition and anxiety after surgery in Zucker rats.

Vulnerable patients are at risk for neuroinflammation-mediated post-operative complications, including depression (POD) and cognitive dysfunction (POCD). Zucker rats, expressing multiple risk factors for post-operative complications in humans, may provide a clinically relevant model to study pathophysiology and explore potential interventions. J147, a newly developed anti-dementia drug, was shown to prevent POCD in young healthy rats, and improved early post-surgical recovery in Zucker rats. Aim of the present study was to investigate POCD and the therapeutic potential of J147 in male Zucker rats. Risk factors in the Zucker rat strain were evaluated by comparison with lean littermates. Zucker rats were subjected to major abdominal surgery. Acute J147 treatment was provided by a single iv injection (10 mg/kg) at the start of surgery, while chronic J147 treatment was provided in the food (aimed at 30 mg/kg/day), starting one week before surgery and up to end of protocol. Effects on behavior were assessed, and plasma, urine and brain tissue were collected and processed for immunohistochemistry and molecular analyses. Indeed, Zucker rats displayed increased risk factors for POCD, including obesity, high plasma triglycerides, low grade systemic inflammation, impaired spatial learning and decreased neurogenesis. Surgery in Zucker rats reduced exploration and increased anxiety in the Open Field test, impaired short-term spatial memory, induced a shift in circadian rhythm and increased plasma neutrophil gelatinase-associated lipocalin (NGAL), microglia activity in the CA1 and blood brain barrier leakage. Chronic, but not acute J147 treatment reduced anxiety in the Open Field test and protected against the spatial memory decline. Moreover, chronic J147 increased glucose sensitivity. Acute J147 treatment improved long-term spatial memory and reversed the circadian rhythm shift. No anti-inflammatory effects were seen for J147. Although Zucker rats displayed risk factors, surgery did not induce extensive POCD. However, increased anxiety may indicate POD. Treatment with J147 showed positive effects on behavioral and metabolic parameters, but did not affect (neuro)inflammation. The mixed effect of acute and chronic treatment may suggest a combination for optimal treatment.

Association between anaesthesia-related factors and postoperative neurocognitive disorder: a post-hoc analysis.

BACKGROUND: Postoperative neurocognitive disorder (pNCD) is common after surgery. Exposure to anaesthetic drugs has been implicated as a potential cause of pNCD. Although several studies have investigated risk factors for the development of cognitive impairment in the early postoperative phase, risk factors for pNCD at 3 months have been less well studied. The aim of this study was to identify potential anaesthesia-related risk factors for pNCD at 3 months after surgery. METHODS: We analysed data obtained for a prospective observational study in patients aged ≥ 65 years who underwent surgery for excision of a solid tumour. Cognitive function was assessed preoperatively and at 3 months postoperatively using 5 neuropsychological tests. Postoperative NCD was defined as a postoperative decline of ≥ 25% relative to baseline in ≥ 2 tests. The association between anaesthesia-related factors (type of anaesthesia, duration of anaesthesia, agents used for induction and maintenance of anaesthesia and analgesia, the use of additional vasoactive medication, depth of anaesthesia [bispectral index] and mean arterial pressure) and pNCD was analysed using logistic regression analyses. Furthermore, the relation between anaesthesia-related factors and change in cognitive test scores expressed as a continuous variable was analysed using a z-score. RESULTS: Of the 196 included patients, 23 (12%) fulfilled the criteria for pNCD at 3 months postoperatively. A low preoperative score on Mini-Mental State Examination (OR, 8.9 [95% CI, (2.8-27.9)], p < 0.001) and a longer duration of anaesthesia (OR, 1.003 [95% CI, (1.001-1.005)], p = 0.013) were identified as risk factors for pNCD. On average, patients scored higher on postoperative tests (mean z-score 2.35[± 3.13]). CONCLUSION: In this cohort, duration of anaesthesia, which is probably an expression of the complexity of the surgery, was the only anaesthesia-related predictor of pNCD. On average, patients' scores on cognitive tests improved postoperatively.

Effect of transcutaneous electrical acupoint stimulation on postoperative cognitive function in older patients with lung cancer: A randomized, double-blind, placebo-controlled trial.

Objective: This trial was to examine the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive function in older patients who underwent thoracoscopic pulmonary resection. Methods: This was a prospective, randomized, double-blind, placebo-controlled study. 128 patients scheduled for surgery were randomly assigned to the TEAS group and sham-TEAS group. A standardized intervention of TEAS or sham-TEAS on the acupoints of Baihui (DU20) and bilateral Neiguan (PC6), Hegu (LI4), and Zusanli (ST36) from 30 min before anesthesia induction until the end of the surgery, combined with a general anesthetic protocol performed in the two groups respectively. The primary outcome was the incidence of postoperative cognitive dysfunction (POCD) assessed via the Montreal Cognitive Assessment (MoCA) scale at each time point. The secondary outcomes included the results of the Mini-Mental State Examination (MMSE) score, the Numerical Rating Scale (NRS) on pain and sleep, the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30), and a chronic pain questionnaire at relative time points. Results: Participants who completed the 12-month trial of the two groups were well-matched in baseline demographic and clinical parameters. At postoperative day 1, day 7, and day 30 time points, the incidence of POCD in the sham-TEAS group was always significantly higher than in the TEAS group (65.4% vs 20%, 43.6% vs 7.3%, 40% vs 3.6%, all P < 0.001). Also, the TEAS group showed better scores of MMSE, sleep, and pain compared with the sham-TEAS group (all P < 0.001). At 6 and 12 months points, the global health scores of the TEAS group were still significantly higher than the sham-TEAS group, and the prevalence of chronic pain was significantly lower than the sham-TEAS group (all P < 0.05). Conclusion: TEAS could effectively improve the postoperative cognitive function and long-term life quality of geriatric patients with lung cancer.

Effects of anesthetic adjunctive agents on postoperative cognitive dysfunction in elderly patients undergoing noncardiac surgery: A Bayesian network meta-analysis.

BACKGROUND: Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial. METHODS: The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta-analysis was performed to quantitatively combine the evidence. RESULTS: A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention. CONCLUSIONS: Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta-analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery.

Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1/M2 Microglia Polarization via Sirt6/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery.

Postoperative cognitive dysfunction (POCD) is a severe neurological complication after anesthesia and surgery. However, there is still a lack of effective clinical pharmacotherapy due to its unclear pathogenesis. Caffeic acid phenethyl ester (CAPE), which is obtained from honeybee propolis and medicinal plants, shows powerful antioxidant, anti-inflammatory, and immunomodulating properties. In this study, we aimed to evaluate whether CAPE mitigated cognitive impairment following anesthesia and surgery and its potential underlying mechanisms in aged mice. Here, isoflurane anesthesia and tibial fracture surgery were used as the POCD model, and H2O2-induced BV2 cells were established as the microglial oxidative stress model. We revealed that CAPE pretreatment suppressed oxidative stress and promoted the switch of microglia from the M1 to the M2 type in the hippocampus, thereby ameliorating cognitive impairment caused by anesthesia and surgery. Further investigation indicated that CAPE pretreatment upregulated hippocampal Sirt6/Nrf2 expression after anesthesia and surgery. Moreover, mechanistic studies in BV2 cells demonstrated that the potent effects of CAPE pretreatment on reducing ROS generation and promoting protective polarization were attenuated by a specific Sirt6 inhibitor, OSS_128167. In summary, our findings opened a promising avenue for POCD prevention through CAPE pretreatment that enhanced the Sirt6/Nrf2 pathway to suppress oxidative stress as well as favor microglia protective polarization.

Caloric Restriction Can Ameliorate Postoperative Cognitive Dysfunction by Upregulating the Expression of Sirt1, MeCP2 and BDNF in the Hippocampal CA1 Region of Aged C57BL/6 Mice.

This study aimed to investigate the impact of caloric restriction (CR) on cognitive function in aged C57BL/6 mice after surgery, as well as the underlying mechanisms. Forty 14-month-old male C57BL/6 mice were randomly assigned to the ad libitum (AL, n = 20) group and the CR (n = 20) group. After feeding for 12 weeks, they were subdivided into four groups: AL control (ALC, n = 10), AL with surgery (ALS, n = 10), CR control (CRC, n = 10), and CR with surgery (CRS, n = 10). The Morris Water Maze (MWM) test was used to assess learning and memory capacity. By using western blot and immunofluorescence, the expression of Sirt1, MeCP2, and BDNF in the hippocampus and hippocampal CA1 region was quantified. According to the behavioral test, the CRC and CRS groups had significantly better learning and memory abilities than the ALC and ALS groups, respectively. Sirt1, MeCP2, and BDNF expression in the hippocampus and CA1 region in the hippocampus of the ALC and CRC groups of mice were correlated with cognitive improvement. In conclusion, CR could enhance the postoperative cognitive function in aged mice, most likely by increasing the expression of Sirt1, MeCP2, and BDNF in the CA1 region of the hippocampus.

The impact of tubeless anesthesia versus intubated anesthesia on cerebral oxygen saturation and postoperative cognitive function in patients undergoing video-assisted thoracoscopic surgery: a randomized trial.

Background: In video-assisted thoracoscopic surgery (VATS), intubated anesthesia may affect cerebral oxygen balance and postoperative cognitive dysfunction (POCD). To avoid complications associated with intubated anesthesia, tubeless strategies have been proposed in recent years, but its effect on cerebral oxygen balance and POCD is still unclear. This prospective study compared the cerebral oxygen saturation and the incidence of POCD in patients undergoing VATS anesthetized with tubeless anesthesia vs. intubated anesthesia. Methods: A total of 60 patients with American Society of Anesthesiologists Standard (ASA) grade I-II who planned to undergo VATS at The First People's Hospital of Yunnan Province between May and October 2021 were selected and divided into non-intubated spontaneous ventilation group (SV group) or intubated mechanical ventilation group (MV group) by random number method. The primary outcome included the incidence of POCD and Mini-Mental State Examination (MMSE) on the 1st before operation and the 4th, 7th, 14th, and 30th day postoperatively, and cerebral oxygen saturation during surgery. Other outcomes of interest include respiratory and hemodynamic parameters, serum concentration of cognitive function related proteins [S100ß, interleukin (IL)-6, IL-1ß, and tumor necrosis factor α (TNF-α)], inflammatory cell counts, perioperative adverse events (arrhythmia, hypoxemia, asphyxia, etc.), postoperative pain scores, etc. Results: The incidence of hypercapnia in the SV group was significantly higher than in the MV group (P<0.001). Cerebral oxygen saturation at intraoperative was significantly higher than that in MV group (P<0.01). There was no significant difference in the incidence of POCD and the expression of cognitive function related proteins between the two groups (P>0.05). Leukocyte and neutrophil counts were significantly higher in the MV group after operation (P<0.05), whilst compared to the MV group, the SV group showed shorter postoperative recovery time, rest time before the first out of bed activity, chest tube duration, as well as less drainage volume of the chest tube and postoperative sore throat rarely occurred (P<0.05). Conclusions: Tubeless VATS can increase the incidence of hypercapnia and intraoperative cerebral oxygen saturation, but has no statistically significant difference in the incidence of POCD. In addition, tubeless anesthesia reduces systemic inflammatory, promotes the early postoperative mobilization, and accelerates the postoperative rehabilitation of patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100042381.

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD), especially in elderly patients, is a serious complication characterized by impairment of cognitive and sensory modalities after surgery. The pathogenesis of POCD mainly includes neuroinflammation, neuronal apoptosis, oxidative stress, accumulation of Aß, and tau hyperphosphorylation; however, the exact mechanism remains unclear. Non-coding RNA (ncRNA) may play an important role in POCD. Some evidence suggests that microRNA, long ncRNA, and circular RNA can regulate POCD-related processes, making them promising biomarkers in POCD diagnosis, treatment, and prognosis. This article reviews the crosstalk between ncRNAs and POCD, and systematically discusses the role of ncRNAs in the pathogenesis and diagnosis of POCD. Additionally, we explored the possible mechanisms of ncRNA-associated POCD, providing new knowledge for developing ncRNA-based treatments for POCD.

Effects of Dexmedetomidine Anesthesia on Early Postoperative Cognitive Dysfunction in Elderly Patients.

The stimulation of tracheal extraction and anesthesia may lead to early postoperative cognitive dysfunction (POCD) in elderly patients, especially within 72 h after surgery, due to the insufficient compensatory and regulatory effects of their cardiovascular system. This study was performed to demonstrate the effects of additional dexmedetomidine (DEX) administration on alleviating early POCD (72 h post intubation) and inflammation in elderly patients who underwent intubation. A parallel-randomized trial was performed in this study. A total of 100 patients aged 60-85 years were randomly divided into two groups (DEX, n = 50; control, n = 50). They received traditional anesthesia and additional DEX medications. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognitive dysfunction of patients. The enzyme-linked immunosorbent assay (ELISA) was used to detect the stress and inflammatory response of the two groups of patients. Administration of DEX significantly improved the MMSE and MoCA scores 24 and 72 h post operation. The S100ß and neuron-specific enolase (NSE) levels in serum were downregulated by DEX 6 and 24 h post operation. The norepinephrine and cortisol levels in serum were downregulated by DEX 15 and 30 min post operation. The interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels in serum were also downregulated by DEX 15 and 30 min post operation. DEX alleviated POCD and inflammation in elderly patients who underwent intubation.

Screening for Mild Cognitive Impairment in the Preoperative Setting: A Narrative Review.

Cognitive impairment predisposes patients to the development of delirium and postoperative cognitive dysfunction. In particular, in older patients, the adverse sequelae of cognitive decline in the perioperative period may contribute to adverse outcomes after surgical procedures. Subtle signs of cognitive impairment are often not previously diagnosed. Therefore, the aim of this review is to describe the available cognitive screeners suitable for preoperative screening and their psychometric properties for identifying mild cognitive impairment, as preoperative workup may improve perioperative care for patients at risk for postoperative cognitive dysfunction. Electronic systematic and snowball searches of PubMed, PsycInfo, ClinicalKey, and ScienceDirect were conducted for the period 2015-2020. Major inclusion criteria for articles included those that discussed a screener that included the cognitive domain 'memory', that had a duration time of less than 15 min, and that reported sensitivity and specificity to detect mild cognitive impairment. Studies about informant-based screeners were excluded. We provided an overview of the characteristics of the cognitive screener, such as interrater and test-retest reliability correlations, sensitivity and specificity for mild cognitive impairment and cognitive impairment, and duration of the screener and cutoff points. Of the 4775 identified titles, 3222 were excluded from further analysis because they were published prior to 2015. One thousand four hundred and forty-eight titles did not fulfill the inclusion criteria. All abstracts of 52 studies on 45 screeners were examined of which 10 met the inclusion criteria. For these 10 screeners, a further snowball search was performed to obtain related studies, resulting in 20 articles. Screeners included in this review were the Mini-Cog, MoCA, O3DY, AD8, SAGE, SLUMS, TICS(-M), QMCI, MMSE2, and Mini-ACE. The sensitivity and specificity range to detect MCI in an older population is the highest for the MoCA, with a sensitivity range of 81-93% and a specificity range of 74-89%. The MoCA, with the highest combination of sensitivity and specificity, is a feasible and valid routine screening of pre-surgical cognitive function. This warrants further implementation and validation studies in surgical pathways with a large proportion of older patients.

Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients after operation. It will prolong the length of stay, reduce the independence and quality of daily life, and increase the risk of death. However, at present, there is a lack of safe and effective ideal drugs for the prevention and treatment of POCD. Melatonin is one of the hormones secreted by the pineal gland of the brain, which has the functions of regulating circadian rhythm, anti-inflammation, anti-oxidation, anti-apoptosis, and so on. Some recent studies have shown that MT can prevent and treat POCD by adjusting circadian rhythm, restoring cholinergic system function, neuroprotection, and so on. This article will introduce POCD, melatonin and the mechanism of melatonin on POCD, respectively, to provide a basis for clinical prevention and treatment of POCD in the elderly.

Systematic review and meta-analysis of the prognostic value of Narcotrend monitoring of different depths of anesthesia and different Bispectral Index (BIS) values for cognitive dysfunction after tumor surgery in elderly patients.

Background: To study the effect of Narcotrend monitoring on the incidence of early postoperative cognitive dysfunction (POCD) under different Bispectral Index (BIS) conditions and the effect of different depths of anesthesia on the incidence of POCD. Methods: We performed a literature search of the PubMed, Embase, OVID (database system made by Ovid Technologies, USA), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Chinese Sci-tech Journals Database, Wanfang Data, etc. from the date of establishment of the database until December 31, 2020. Results: In the end, eighty articles were included, with a total of 714 patients. The meta-analysis results showed that four articles (255 patients) compared the state of deep anesthesia (BIS 30-40) with conventional anesthesia (BIS 40-60 earlier) after POCD. Also, the incidence of POCD on the first day after deep anesthesia [Narcotrend stage (NTS): negative correlation is currently the most appropriate egg description; Nd can subdivide the original electroencephalogram (EEG) into six stages 15 levels (Nd Sg, NTS), or A (state of wakefulness), state B0-B2 (sedated state), state C0-C2 (light anesthetic state), state D0-D2 (general anesthesia), state E0-E2 (deep anesthesia state), and state F0-F2 (burst suppression state)] was significantly lower than that of conventional anesthesia (NTS D0-D1) [odds ratio (OR) =0.21, 95% confidence interval (CI): 0.13-0.35, P<0.00001]. Moreover, the incidence of POCD in deep anesthesia (NTS E1) at 7 days after surgery was significantly lower than that of conventional anesthesia (NTS D0) (OR =0.45, 95% CI: 0.23-0.91, P=0.03), while the incidence of POCD 7 days after NTS D2 in conventional anesthesia was significantly lower than that of NTS D0 (OR =0.42, 95% CI: 0.24-0.71, P=0.001). Discussions: POCDs are thought to be the result of a combination of physical defects and precipitating factors in patients with their own physical impairments, and despite potential adverse effects, there is currently no consensus on the incidence of POCDs in patients with tumor, current risk factors, causes, and prevention strategies. Moreover, the level of evidence is low, and the deviation between different studies cannot be ruled out.

Intervention of NF-Κb Signaling Pathway and Preventing Post-Operative Cognitive Dysfunction as Well as Neuronal Apoptosis.

BACKGROUND: The Postoperative cognitive dysfunction (POCD) model was constructed by resection of the left hepatic lobe in aged mice to determine the behavioral effects of the POCD model in aged mice and the relationship between NF-κB and POCD in apoptosis and autophagy. Provide a theoretical basis for POCD prevention and treatment. METHODS: This study was carried out in Ningbo No. 6 Hospital, Zhejiang, China, from Jun 2019 to Dec 2020. The POCD model was constructed after resection of the left extrahepatic lobe in aged mice and randomly divided into 6 groups: sham operation group, operation group (normal saline control group, solvent group, YC-1 group, PDTC group and 3-MA group). Related indicators of behavioral changes, neuronal inflammatory responses, apoptosis, and autophagy were examined. RESULTS: The escape latency of the aged mice in the surgical group was significantly prolonged at three time points compared with the control group, and the number of insertions decreased significantly. Microglia are activated and the inflammatory response is increased, whereas PDTC has an inhibitory effect. It was demonstrated that apoptosis and necrosis of neurons can be induced by the NF-κb pathway, and autophagy can be promoted, whereas autophagy occurs before apoptosis. CONCLUSION: Activation of NF-κb pathway in neurons after POCD causes neuronal apoptosis and autophagy, and cognitive impairment occurs. PDTC, a NF-κb pathway inhibitor, can effectively reduce neuronal apoptosis induced by secondary brain injury after POCD. Necrosis, to protect the brain tissue.

Effects of anesthetics on expression of dopamine and acetylcholine receptors in the rat brain in vivo.

Dopamine D2 and acetylcholine M1 receptors might be related to post-operative cognitive dysfunction. The aim of the present study is to investigate whether several anesthetics which are used for general anesthesia and/or sedation, affect expression of dopamine D2 and acetylcholine M1 receptors in the rat brain. Thirty-six male rats aged 5-9 weeks old were divided into six groups (n = 6 in each group); five groups for anesthetics and one for control. The five groups were anesthetized with either dexmedetomidine 0.4 µg/kg/min, propofol 50 mg/kg/h, midazolam 25 mg/kg/h, sevoflurane 3.3%, or nitrous oxide 75% for 4 h. Then, the rats were decapitated, and the cerebral cortex, hippocampus, corpus striatum, brain stem, and cerebellum were collected from all rats. Then, real-time polymerase chain reaction was performed to examine the expression of Drd2 (cord dopamine D2 receptor) and Chrm1 (cord acetylcholine M1 receptor). There were no significant differences among the groups regarding Drd2 and Chrm1 mRNA expression of each region of the brain. Postsynaptic changes of dopamine D2 and acetylcholine M1 receptors due to administration of dexmedetomidine, propofol, midazolam, sevoflurane, and nitrous oxide are unlikely to occur at the doses of each anesthetic used in the present study.

Pleiotrophin Potentiates Sevoflurane Anesthesia-induced Learning Deficits in Mice.

Postoperative cognitive dysfunction (POCD) is a major postoperative neurological complication in children and the elderly. However, the detailed mechanisms underlying this process remain unclear. This study aims to investigate the effect of pleiotrophin on sevoflurane-induced neuroinflammation and cognitive impairment. The novel object recognition test was performed to evaluate the cognitive and motor function of aged C57BL/6 (wild-type, WT) and pleiotrophin-knockout mice treated with sevoflurane. Small molecule inhibitors targeting receptor protein tyrosine phosphatase (RPTP) ß/ζ, a pleiotrophin receptor, were used to ameliorate cognitive dysfunction. Sevoflurane treatment induced cognitive dysfunction and motor impairment in aged WT mice. Sevoflurane anesthesia induced the upregulation of certain inflammatory cytokines. Pleiotrophin knockout ameliorated the sevoflurane-induced cognitive dysfunction and motor impairment in vivo. Treatment with small molecule inhibitors targeting RPTP ß/ζ inhibited sevoflurane-induced neuroinflammation. In summary, pleiotrophin was shown to potentiate sevoflurane anesthesia-induced cognitive dysfunction and learning deficits in mice.

Perioperative probiotics attenuates postoperative cognitive dysfunction in elderly patients undergoing hip or knee arthroplasty: A randomized, double-blind, and placebo-controlled trial.

Background: Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients following surgery. The preventive and/or treatment strategies for the incidence remain limited. Objective: This study aimed to investigate the preventive effect of perioperative probiotic treatment on POCD in elderly patients undergoing hip or knee arthroplasty. Methods: After obtaining ethical approval and written informed consent, 106 patients (age ≥60 years) were recruited, who scheduled elective hip or knee arthroplasty, from 16 March 2021 to 25 February 2022 for this randomized, double-blind, and placebo-controlled trial. They were randomly assigned with a 1:1 ratio to receive either probiotics or placebo treatment (four capsules, twice/day) from hospital admission until discharge. Cognitive function was assessed with a battery of 11 neuropsychological tests on the admission day and the seventh day after surgery, respectively. Results: A total of 96 of 106 patients completed the study, and their data were finally analyzed. POCD occurred in 12 (26.7%) of 45 patients in the probiotic group and 29 (56.9%) of 51 patients in the placebo group (relative risk [RR], 0.47 [95% confidence interval [CI], 0.27 to 0.81]; P = 0.003). Among them, mild POCD occurred in 11 (24.4%) in the probiotic group and 24 (47.1%) in the placebo group (RR, 0.52 [95% CI, 0.29 to 0.94]; P = 0.022). No significant difference in severe POCD incidence was found between the two groups (P = 0.209). Compared with the placebo group, the verbal memory domain cognitive function was mainly improved in the probiotic group. Conclusion: Probiotics may be used perioperatively to prevent POCD development and improve verbal memory performance in elderly patients receiving hip or knee arthroplasty. Clinical trial registration: www.chictr.org.cn, identifier: ChiCTR2100045620.

Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids.

Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (ß-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.