Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Role of PI3K/Akt/mTOR signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The rats received laparotomy under 3% sevoflurane anesthesia in O, E and LY groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the tail vein in group LY. Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats. The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), synaptophysin (SYP) and postsynaptic density protein 95 (PSD 95) (by Western blot ) and dendrite length in hippocampal CA1 area (using Golgi staining). The density of dendrites was calculated. Results:There were no statistically significant differences in exercise speed, distance, and time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of neurons in hippocampal CA1 region was prolonged, and the density of neurons in hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group LY ( P<0.05). Conclusions:The mechanism by which edaravone reduces postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving synaptic plasticity in aged rats.

Risk factors for postoperative cognitive dysfunction and the predictive model in elderly patients undergoing lumbar surgery under general anesthesia / 中华麻醉学杂志

Objective:To identify the risk factors for postoperative cognitive dysfunction (POCD) and develop the prediction model in elderly patients undergoing lumbar surgery under general anesthesia.Methods:The elderly patients undergoing elective lumbar surgery under general anesthesia in our hospital from July 2021 to July 2022 were enrolled. Cognitive function was assessed at 7 days after surgery using Mini-Mental State Examination and Montreal Cognitive Assessment. When the decrease in both scales≥ 1 standard deviation, the patients were considered as having POCD. The patients were divided into POCD group and non-POCD group according to whether POCD developed. The propensity score matching was used to balance the confounding bias between two groups. The multivariate logistic regression analysis was used to identify the risk factors for POCD. The prediction model was constructed, and a nomogram was drawn for visualization of the model. The receiver operating characteristic curve, calibration plot and decision curve analysis (DCA) were drawn to evaluate the differentiation, consistency and clinical validity of the model, respectively.Results:A total of 159 patients were enrolled in this study, and the incidence of POCD was 31.4%. There were statistically significant differences in the ratio of intraoperative blood transfusion, cumulative time of hypotension, total infusion volume and operation time between two groups ( n=32 each) after propensity score matching ( P<0.05). The results of multivariate logistic regression showed that age, educational levels, diabetes mellitus, previous two or more operations under general anesthesia, APTT and cumulative time of hypotension were independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia ( P<0.05). A model was developed based on the risk factors mentioned above: LogitP=-15.878+ 0.263 × Age (years) - 0.122 × Educational Level (years)+ 1.601 × Diabetes Mellitus+ 1.468 × History of General Anesthesia for 2 or more times+ 0.608 × Cumulative Time of Hypotension(min) - 0.140 × APTT (s). The area under the receiver operating characteristic curve was 0.930 (95% CI 0.887-0.973), the sensitivity was 0.920, specificity was 0.798 and Youden index was 0.718. After visualizing the model via nomogram, the model was verified by Hosmer-Lemeshow test, P=0.403, C index was 0.930, and corrected C index was 0.914. Conclusions:Age, educational levels, diabetes mellitus, previous multiple operations under general anesthesia, APTT and cumulative time of hypotension are independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia, and the established risk prediction model can effectively predict the occurrence of POCD in elderly patients undergoing lumbar surgery under general anesthesia.

Effect of exosomes derived from bone mesenchymal stem cells on postoperative cognitive function and SIRT1/NF-κB signaling pathway in aged mice / 中华麻醉学杂志

Objective:To evaluate the effect of exosomes derived from bone mesenchymal stem cells (BMSCs-EXO) on the postoperative cognitive function and silent infomation regulator 1 (SIRT1)/ nuclear factor kappa B (NF-κB) signaling pathway in aged mice.Methods:BMSCs-EXO were isolated by differential centrifugation method and then identified. Twenty healthy male C57BL/6 aged mice, aged 18 months, weighing 35-40 g, were divided into 4 groups ( n=5 each) using a random number table method: sham operation group (Sham group), operation group (O group), BMSCs-EXO group and EX527 (SIRT1 inhibitor)group. The abdomen regions were shaved for sterilization without exploratory laparotomy in Sham group. Exploratory laparotomy was performed in O group. BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in BMSCs-EXO group. EX527 5 mg/kg was intraperitoneally injected daily at 1-3 days before surgery, and BMSCs-EXO 50 μg was injected through the tail vein at 1 h before surgery in EX527 group. Morris water maze test was used to evaluate the learning and memory ability for 5 consecutive days staring from the 1st day after surgery. Mice were sacrificed at 1 h after the end of Morris water maze test on day 5 after surgery, and the hippocampal tissues were collected for observation of the pathological changes of hippocampal CA1 region and for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA (quantitative real-time polymerase chain reaction) and SIRT1 and NF-κB p65 (by Western blot). Results:Compared with Sham group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were found in O group. Compared with O group, the escape latency was significantly shortened, the times of original platform crossing were increased, the swimming time spent in the original platform quadrant was prolonged, the expression of TNF-α, IL-6 and IL-1β mRNA was down-regulated, the expression of SIRT1 was up-regulated, the expression of NF-κB p65 was down-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were significantly attenuated in BMSCs-EXO group ( P<0.05). Compared with BMSCs-EXO group, the escape latency was significantly prolonged, the times of original platform crossing were decreased, the swimming time spent in the original platform quadrant was shortened, the expression of TNF-α, IL-6 and IL-1β mRNA was up-regulated, the SIRT1 expression was down-regulated, the NF-κB p65 expression was up-regulated ( P<0.05), and the pathological changes of hippocampal tissues in CA1 region were accentuated in EX527 group. Conclusions:BMSCs-EXO can improve the postoperative cognitive function in aged mice, and the mechanism may be associated with the activation of SIRT1/NF-κB signaling pathway.

Relationship between hippocampal miR-3065-5p and IGF-1/PI3K/Akt signaling pathway in a mouse model of perioperative neurocognitive disorder / 中华麻醉学杂志

Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.

Effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy / 中华麻醉学杂志

Objective:To evaluate the effect of Mongolian medicine Eerdun Wurile on postoperative cognitive function in elderly patients undergoing thoracoscopic lobectomy.Methods:Sixty elderly patients of either gender, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index≤28 kg/m 2, with preoperative Mini-Mental State Examination (MMSE) score ≥27 points, undergoing thoracoscopic lobectomy under general anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and Eerdun Wurile group (group E). Eerdun Wurile 15 capsules per day were taken for 7 consecutive days starting from 3 days before surgery in group E, and placebo was given instead in group C. The peripheral venous blood samples were collected before medication at 3 days before surgery (T 1) and 24 and 72 h after surgery (T 2, 3) for determination of the concentrations of serum brain-derived neurotrophic factor (BDNF), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Tau proteins by enzyme-linked immunosorbent assay. The patients′ cognitive function was assessed by MMSE at T 1 and 5 days after surgery (T 4), and the occurrence of cognitive decline (MMSE score < 27) was recorded. Results:Compared with group C, the serum BDNF concentration was significantly increased at T 2 and T 3, and the concentrations of IL-1β, TNF-α and Tau protein were decreased, the MMSE score was increased at T 4, and the incidence of cognitive decline was decreased in group E ( P<0.05). Conclusions:Mongolian medicine Eerdun Wurile can improve postoperative cognitive function in elderly patients undergoing thoracoscopic surgery, and the mechanism may be related to reduction of systemic inflammatory responses and promotion of nerve cell repair and regeneration.

Correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction in elderly patients undergoing surgery / 中国医师杂志

Objective:To investigate the correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction (POCD) in elderly patients undergoing surgery.Methods:A total of 119 elderly patients who underwent elective spinal surgery in the Second Hospital of Shanxi Medical University from January 2021 to January 2022 were selected and scored on the Montreal Cognitive Assessment (MoCA) Scale 1 day before surgery and 1, 7 and 21 days after surgery. The selected patients were divided into POCD group (51 cases) and non-POCD group (68 cases) according to whether the MoCA Scale score decreased ≥2 points 1 day before surgery and 1 day after surgery. S100-β, neuron-specific enolase (NSE) levels and serum exosome miR-29C expression levels were detected and analyzed in all patients 1 day before and 1 day after surgery. Pearson correlation analysis showed the correlation between MoCA Scale score and S100-β, NSE and miR-29C. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of S100-β, NSE and miR-29C for POCD occurrence in elderly patients undergoing surgery.Results:The score of MoCA Scale in POCD group were significantly decreased 1, 7 and 21 days after surgery compared with 1 day before surgery (all P<0.05), while the score of MoCA Scale in non-POCD group were significantly decreased only 1 day after surgery compared with 1 day before surgery ( P<0.05). The levels of S100-β and NSE and the expression level of serum exosome miR-29C in 2 groups were significantly increased 1 day after surgery compared with 1 day before surgery (all P<0.05). Moreover, the levels of S100-β and NSE and the expression level of serum exosome miR-29C in POCD group were significantly higher than those in non-POCD group 1 day after surgery (all P<0.05). There was a negative correlation between the MoCA Scale score and the expression level of serum exosome miR-29C 1 day after surgery in the POCD group ( P<0.05). ROC curve analysis showed that the expression levels of NSE, S100-β and exosome miR-29C 1 day after surgery predicted the risk of POCD in elderly surgical patients with area under the curve (AUC) of 0.891, 0.908 and 0.918, respectively. Conclusions:The occurrence of POCD in elderly patients with surgery is related to the increase of the expression level of serum exosome miR-29C, and the expression level of serum exosome miR-29C is negatively correlated with MoCA Scale score. Early monitoring of the miR-29C expression level can provide a basis for the occurrence and development of postoperative POCD in elderly patients, disease diagnosis and clinical intervention.

Progress on the researches of acupuncture preconditioning before surgery / 中国针灸

This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.

Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy / 中南大学学报(医学版)

OBJECTIVES@#Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation.@*METHODS@#This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation.@*RESULTS@#Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05).@*CONCLUSIONS@#Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

The postoperative cognitive dysfunction induced by central inflammation with possible involvement of the gut-brain axis

Abstract Background: Postoperative cognitive dysfunction is widely recognized as severe postoperative central nervous dysfunction and has a significant impact on the 'patient's physical and mental health. Methods: Postoperative models of tibial fracture in aged rats were established, including the control group, model group, CCL11 protein injection group, and saline injection group. Morris water maze test was used to detect the behavioral characteristics of rats. Enzyme-Linked Immunosorbent Assay was used or determine the content of CCL11 and CXCL10. Immunofluorescence staining was used to detect the distribution of CD14+CD163+macro-phages in colon tissues and CD11b+CCR3+microglia cells in hippocampal tissues. Western blot analyzed NOX1 and STAT3 expression in hippocampus tissues. Results: Water maze test results confirmed severe cognitive impairment in CCL11 rats. The content of CCL11 and CXCL10 in the CCL11 group was much higher than that of the model group. The distribution of macrophage and microglia cells in the CCL11 model group was greater than that in the model group and the saline group. The expression of NOX1 and STAT3 in the CCL11 group was higher compared with the model group. Conclusion: Abnormal macrophage function and excessive CCL11 secretion were observed in the rats with lower limb fractures after surgery. Postoperative central inflammation in rats with lower limb fracture induced postoperative cognitive dysfunction through the gut-brain axis molecular mechanism.

Long-Term Neurophysiological Outcomes in Patients Undergoing Coronary Artery Bypass Grafting

Abstract Introduction: This study aims to evaluate late postoperative neurophysiological outcomes in patients after coronary artery bypass grafting (CABG). Methods: Forty-five male patients with stable coronary artery disease aged 45-69 years underwent extended neuropsychological assessment using the software Status PF and electroencephalographical examination 3-5 days before CABG and 5-7 years after CABG. Postoperative decline in cognitive functions was determined by a 20% decrease in the cognitive indicator compared to that at baseline on 20% of the tests included in the Status PF battery. Statistical analysis was performed using the software STATISTICA 10.0. Multiple regression was used to identify demographic, clinical, and electroencephalographical variables associated with adverse cognitive outcomes. Results: Cognitive decline was observed in 54% of the patients in the long-term postoperative period. Five to seven years after CABG, all patients have shown an increase in the theta rhythm power compared to the preoperative values, which is most pronounced in the frontal and temporal areas of the right hemisphere (P=0.04), along with a decrease in the alpha rhythm in the posterior areas of the cortex (P=0.005). Multiple regression has reported that the main predictors of cognitive impairment are slower mean alpha frequency, decreased theta-2 rhythm with eyes closed in the right temporal area, and increased theta-2 rhythm with eyes open in the left temporal area (F(5.39)=8.81; P<0.00007; adjusted R-squared=0.57). Conclusion: Our findings indicate that 54% of the patients suffer from postoperative cognitive decline associated with increased theta and decreased alpha rhythms 5-7 years after CABG.

Effect of electroacupuncture pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction (POCD) and explore the relevant mechanism of EA pretreatment on the improvement of learning and memory in POCD aged mice.@*METHODS@#A total of 72 healthy male aged mice were randomized into a blank group, a model group, a medication group and an EA group, 18 mice in each one. In each group, 1-day, 3-day and 7-day subgroups were divided separately, 6 mice in each subgroup. In the EA group, "Baihui" (GV 20) and "Dazhui" (GV 14) were selected and stimulated with EA, using continuous wave (15 Hz, 1 mA), continuously for 30 min, once a day, for 5 days consecutively. In the medication group, 10% minocycline was injected intraperitoneally, 40 mg/kg, once a day, consecutively for 5 days. In the blank and the control group, intraperitoneal injection of 0.9% sodium chloride solution was given with equal dosage. Except the blank group, at the end of intervention, partial hepatectomy was conducted to establish POCD model in the rest groups. Morris water maze test was adopted to evaluate the learning and memory ability of the aged mice. ELISA was used to determine the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampal tissue. Western blot method was applied to detect the protein expressions of superoxide dismutase 1 (SOD 1) and superoxide dismutase 2 (SOD 2) in the hippocampal tissue.@*RESULTS@#Compared with the blank group, the percentage of platform quadrant residence time was obviously reduced in the mice in the model group (@*CONCLUSION@#Electroacupuncture pretreatment at "Baihui" (GV 20) and "Dazhui" (GV 14) may increase the learning and memory ability of POCD aged mice, which is probably related to the decrease of oxidative stress and the strengthening of hippocampal antioxidant capacity.

S100B level and cognitive dysfunction after robotic-assisted laparoscopic radical prostatectomy procedures: a prospective observational study / Nível de S100B e disfunção cognitiva após prostatectomia radical laparoscópica assistida por robô: estudo observacional prospectivo

Abstract Background: The present study investigated the association between Postoperative Cognitive Dysfunction (POCD) and increased serum S100B level after Robotic-Assisted Laparoscopic Radical Prostatectomy (RALRP). Methods: The study included 82 consecutive patients who underwent RALRP. Serum S100B levels were determined preoperatively, after anesthesia induction, and at 30 minutes and 24 hours postoperatively. Cognitive function was assessed using neuropsychological testing preoperatively, and at 7 days and 3 months postoperatively. Results: Twenty four patients (29%) exhibited POCD 7 days after surgery, and 9 (11%) at 3 months after surgery. Serum S100B levels were significantly increased at postoperative 30 minutes and 24 hours in patients displaying POCD at postoperative 7 days (p = 0.0001 for both) and 3 months (p = 0.001 for both) compared to patients without POCD. Duration of anesthesia was also significantly longer in patients with POCD at 7 days and 3 months after surgery compared with patients without POCD (p = 0.012, p = 0.001, respectively), as was duration of Trendelenburg (p = 0.025, p = 0.002, respectively). Composite Z score in tests performed on day 7 were significantly correlated with duration of Trendelenburg and duration of anesthesia (p = 0.0001 for both). Conclusions: S100B increases after RALRP and this increase is associated with POCD development. Duration of Trendelenburg position and anesthesia contribute to the development of POCD. Trial Registry Number: Clinicaltrials.gov (N° NCT03018522).

Resumo Introdução: O presente estudo investigou a associação entre Disfunção Cognitiva Pós-Operatória (DCPO) e aumento do nível sérico de S100B após Prostatectomia Radical Laparoscópica Assistida por Robô (PRLAR). Métodos: O estudo incluiu 82 pacientes consecutivos submetidos à PRLAR. Os níveis séricos de S100B foram determinados: no pré-operatório, após indução anestésica, e aos 30 minutos e 24 horas do pós-operatório. A função cognitiva foi avaliada com testes neuropsicológicos no pré-operatório, no 7° dia pós-operatório (7 DPO) e aos 3 meses após a cirurgia (3 MPO). Resultados: Observamos 24 pacientes (29%) com DCPO no 7 DPO e 9 pacientes com DCPO (11%) após 3 meses da cirurgia. Quando comparados com os pacientes sem DCPO, os níveis séricos de S100B estavam significantemente aumentados aos 30 minutos e às 24 horas do pós-operatório nos pacientes que apresentaram DCPO no 7 DPO (p= 0,0001 para os dois momentos) e 3 meses após a cirurgia (p= 0,001 para os dois momentos) A duração anestésica também foi significantemente maior em pacientes com DCPO no 7 DPO e 3 MPO em comparação com pacientes sem DCPO (p= 0,012, p= 0,001, respectivamente), assim como a duração da posição de Trendelenburg (p= 0,025, p= 0,002, respectivamente). O escore Z composto nos testes realizados no 7 DPO foi significantemente correlacionado com a duração da posição de Trendelenburg e a duração da anestesia (p= 0,0001 para ambos). Conclusão: S100B aumenta após PRLAR e o aumento está associado ao desenvolvimento de DCPO. A duração anestésica e o tempo decorrido em posição de Trendelenburg contribuem para o desenvolvimento de DCPO. Número de registro do estudo: Clinicaltrials.gov (n° NCT03018522)

Effects of sevoflurane on the cognitive function and the quantity of alpha 7 nicotinicacetycholine receptors in the hippocampus of elderly model rats / 医学研究生学报

ObjectiveSome studies reported that α7nAChR is closely related to the cognitive function. However, the elderly patients have become a high-risk group of postoperative cognitive dysfunction. The aim of this study was to explore the effect of sevoflurane inhalation on the cognitive function and the quantity of alpha 7nicotinic acetycholine receptors in the hippocampus of elderly model rats.MethodsAdult male Sprague-Dawley rats (N=72) were given subcutaneous injection of D-galactose on the neck for 6 weeks to establish elderly models. The model rats were divided into 4 groups randomly: control group (group Con, n=18) with 6h exposure carrier gas (2L/min Air+2L/min O2); Sevoflurane group (group Sev, n=18) with 6 h exposure to 3.2% sevoflurane through carrier gas. Sev+α7nAChR antagonist group (group Sev+M) injected with methyllycaconitine, after 24 h inhaled of 3.2% sevoflurane and carrier gas for 6 h. Sev+α7nAChR agonist group (group Sev+P, n=18) injected with PNU-282987, after 24 h inhaled of 3.2% sevoflurane and carrier gas for 6 h. Morris water maze experiments were conducted on 6 rats in each group 2 h, 1 week and 4 weeks after treatments, respectively. Every cycle after the behavioral test, the hippocampi were taken out. RT-qPCR method was used to detect α7nAChR mRNA expression. Western blotting was used to detect α7nAChR proteins expression.ResultsBehavioral test: compared with Con group at 2 h after awakening, indicators of working memory and spatial probe test in Sev group and Sev+M group decreased significantly (P0.05). RT-qPCR: compared with Con group at 2 h and 1 w after awakening, the expression of alpha 7nAChR mRNA in the other groups was down-regulated, while at 4 w it was up-regulated (P<0.05).Western blot: protein expression of alpha 7nAChR was down-regulated in the 2 h, 1 w Sev group and the Sev+M group after awakening, and up-regulated in the 4 w group after awakening (P<0.05).ConclusionInhalation of 3.2% sevoflurane for 6 h can cause 7nAChR metabolic disturbance in hippocampus of aging model rats and lead to a short-term (1 w) decline in learning and memory ability of the rats, but this effect is reversible. The PNU-282987 agonist can alleviate the temporary decrease of learning and memory caused by sevoflurane.

Progress on the roles of glia in postoperative cognitive dysfunction / 生物医学工程学杂志

Postoperative cognitive dysfunction (POCD) is one of the most common complications after surgery under general anesthesia and usually manifests as newly presented cognitive impairment. However, the mechanism of POCD is still unclear. In addition to neurons, glial cells including microglia, astrocytes and oligodendrocytes, represent a large cell population in the nervous system. The bi-directional communication between neurons and glia provides basis for neural circuit function. Recent studies suggest that glial dysfunctions may contribute to the occurrence and progress of POCD. In this paper, we review the relevant work on POCD, which may provide new insights into the mechanism and therapeutic strategy for POCD.

Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en Bucaramanga (Santander, Colombia) en el año 2017 / Postoperative cognitive dysfunction incidence for regional and general anesthesia in a level four institution in Bucaramanga (Santander, Colombia) during 2017 / Incidência do déficit cognitivo pós-operatório em anestesia regional e geral em uma instituição de quarto nível em Bucaramanga (Santander, Colômbia) em 2017

Introducción. En el proceso de envejecimiento, la mayoría de los sistemas orgánicos mantienen su funcionamiento basal, pero existe una reducción de la reserva funcional y de la capacidad para compensar el estrés fisiológico, lo que hace que los pacientes de mayor edad sean más propensos a complicaciones postoperatorias. Se realizó un estudio en instituciones de Bucaramanga para determinar la incidencia de déficit cognitivo postoperatorio y los factores de riesgo asociados. Metodología. Estudio observacional analítico de cohorte prospectivo realizado en instituciones de salud de Bucaramanga durante 2017 con pacientes mayores de 55 años intervenidos bajo anestesia regional, general balanceada o anestesia total intravenosa. Resultados. Se estudiaron 173 pacientes, 112 mujeres (64.74%) y 61 hombres (35.26%) operados. Las técnicas anestésicas más empleadas fueron: Regional (46.24%) y General balanceada (44.51%). La incidencia de Déficit Cognitivo Postoperatorio a corto plazo fue 6.36% en pacientes previamente sanos, con valor P significativo (0.001) ajustado. Se detectó deterioro cognitivo del 51.41% con alteraciones en los dominios de lenguaje, atención y memoria; con aumento en la evaluación a largo plazo. Durante el seguimiento de pacientes a largo plazo resultó en un 11.55%, determinando la incidencia de Déficit Cognitivo Postoperatorio tardío en un 17.91%. La técnica anestésica con mayor proporción de déficit a largo plazo fue la anestesia mixta, comparada con anestesia regional. Discusión. En la actualidad no existe una definición estandarizada de Déficit Cognitivo Postoperatorio, se ha observado mayor frecuencia y mayor prolongación en pacientes de edad avanzada. El estudio demostró una incidencia temprana significativamente menor, comparándolo con artículos internacionales, pero una incidencia mayor en déficit postoperatorio tardío, resultado de mayores complicaciones intraoperatorias, comparado con otros estudios. Conclusiones. El Déficit Cognitivo Postoperatorio involucra múltiples factores de riesgo; en el estudio se encontró mayor asociación con la edad, la escolaridad, la hipotensión y la anestesia general. No hubo asociación entre comorbilidades y el Déficit Cognitivo Postoperatorio. Se determinó la presencia de hipotensión para desarrollo de este déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

Introduction. Within the aging process, most organic systems maintain their basal functions. However, there is a reduction in functional reserve and the capacity to compensate physiological stress, which makes older patients more prone to postoperative complications. A study was performed in institutions in Bucaramanga to determine the incidence of postoperative cognitive dysfunction and the associated risk factors. Methodology. This was a analytical observational prospective cohort study performed in healthcare institutions in Bucaramanga in 2017 with patients older than 55 years of age under regional, balanced general or total intravenous anesthesia. Results. One hundred and seventy-three operated patients were studied, among which 112 (64.74%) were women and 61 (35.26%) were men. The most commonly used anesthetic techniques were: regional (46.24%) and balanced general (44.51%). Short-term Postoperative Cognitive Dysfunction incidence was 6.36% in previously healthy patients, with an adjusted significant P value (0.001). Cognitive deterioration was detected in 51.41% of patients, with alterations in their mastery of language, attention and memory. This increased for the long-term evaluation. During long-term patient follow-up, it resulted in 11.55%, determining the incidence of delayed Postoperative Cognitive Dysfunction at 17.91%. The anesthetic technique with the highest proportion of long- term dysfunction was mixed anesthesia, compared to regional anesthesia. Discussion. There is currently no standardized definition for Postoperative Cognitive Dysfunction. It has been observed more frequently and for longer extensions in older patients. The study demonstrated a significantly lower early incidence when compared to international articles, but a greater incidence of delayed postoperative dysfunction as a result of more intraoperative complications compared to other studies. Conclusions. Postoperative Cognitive Dysfunction involves multiple risk factors. The study observed a greater association with age, level of education, hypotension and general anesthesia. There was no association between comorbidities and Postoperative Cognitive Dysfunction. The presence of hypotension was determined for developing this dysfunction. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

Introdução. No processo de envelhecimento, a maioria dos sistemas orgânicos mantém seu funcionamento basal, mas há uma diminuição da reserva funcional e da capacidade de compensar o estresse fisiológico que torna os pacientes idosos mais sujeitos a complicações pós-operatórias. Foi realizado um estudo em instituições da cidade de Bucaramanga para determinar a incidência de déficit cognitivo pós-operatório e os fatores de risco associados. Métodos. Estudo observacional analítico de coorte prospectivo realizado em instituições de saúde em Bucaramanga durante o ano de 2017 em pacientes com idade superior a 65 anos operados sob anestesia regional, geral balanceada ou anestesia geral intravenosa. Resultados. Foram estudados 173 pacientes, 112 mulheres (64.74%) e 61 homens (35.26%) operados. As técnicas anestésicas mais utilizadas foram: regional (46.24%) e geral balanceada (44.51%). A incidência de déficit cognitivo pós-operatório de curto prazo foi de 6.36% em pacientes previamente saudáveis, com um valor P significativo (0.001) ajustado. Detectou- se deterioração cognitiva de 51.41% com alterações nos domínios da linguagem, atenção e memória; com aumento na avaliação de longo prazo. No seguimento a longo prazo dos pacientes resultou em 11.55%, determinando a incidência de déficit cognitivo pós-operatório tardio em 17.91%. A técnica anestésica com maior proporção de déficit no longo prazo foi a anestesia mista, em comparação com a anestesia regional. Discussão. Atualmente não existe uma definição padronizada de Déficit Cognitivo Pós-operatório, a qual observa-se com maior frequência e por mais tempo em pacientes idosos. O estudo demonstrou incidência precoce significativamente menor, em comparação com resultados de artigos internacionais, mas maior incidência de déficit pós-operatório tardio, resultado de maiores complicações intraoperatórias, em comparação com outros estudos. Conclusões. O Déficit Cognitivo Pós-operatório envolve múltiplos fatores de risco; o estudo encontrou maior associação com idade, escolaridade, hipotensão e anestesia geral. Não houve associação entre comorbidades e Déficit Cognitivo Pós-operatório. Determinou-se a presença de hipotensão para o desenvolvimento desse déficit. Cómo citar: Contreras-Forero FJ, Ochoa ME, Perez M, Pinillos M, Celis L, Valencia-Guampe JS, et al. Incidencia del déficit cognitivo postoperatorio en anestesia regional y general en una institución de cuarto nivel en bucaramanga (santander, colombia) en el año 2017. MedUNAB. 2020;23(3): 450-463. Doi: https://doi.org/10.29375/01237047.3711

The correlation between orexin-A and early postoperative cognitive function in elderly patients undergoing lumbar surgery under general anesthesia / 解放军医学杂志

Objective To analyze the correlation between serum orexin-A (OXA) and early postoperative cognitive function in elderly patients undergoing lumbar spinal surgery under general anesthesia. Methods A total of 76 elderly patients (age ≥65 years) underwent lumbar spine surgery under general anesthesia from December 2018 to December 2019 in the Affiliated Hospital of Inner Mongolia Medical University were collected. All the enrolled patients were evaluated by the same doctor with the Montreal cognitive assessment scale (MoCA) on one day before the surgery and one to three days after the surgery, and venous blood was extracted from the patient on the operation day and one day after the operation, and the serum levels of OXA and S100β were measured by ELISA. According to the results of cognitive function assessment, the patients were divided into postoperative cognitive dysfunction (POCD) group and non-postoperative cognitive dysfunction (NPOCD) group. The differences in serum OXA and S100β protein levels between the two groups and their correlation with MoCA scores were statistically analyzed. Results There was no statistically significant difference in the MoCA score, serum OXA level, and S100β protein level before surgery, and heart rate (HR), mean artery pressure (MAP), bispectral index (BIS) and pulse oxygen saturation (SpO2) levels before anesthesia induction (T0), at the start of surgery (T1), at 1h after the start of surgery (T2), at the withdrawal time (T3), and at 15 minutes after extubation (T4) between the two groups (P>0.05). At the first, second, and third day after operation, the MoCA scores of the POCD group were lower than those before the operation, and they were both lower than those of the NPOCD group, the difference was statistically significant (P<0.001). There was a statistically significant difference in serum OXA levels between the two groups after the operation (P<0.05). The postoperative S100β protein level was higher than that before the operation in the two groups, and the POCD group increased more significantly, the difference between the two groups after the operation was statistically significant (P<0.05). The postoperative OXA level was positively correlated with the MoCA score (r=0.545, 0.531, 0.779) and negatively correlated with the S100β protein level (r=-0.591, -0.362, -0.743) in the two groups, and the difference was statistically significant (P<0.05). Conclusions The level of serum OXA is positively correlated with early postoperative cognitive function in elderly patients undergoing lumbal spine surgery under general anesthesia, suggesting that OXA may be a potential target for reducing the risk of postoperative cognitive dysfunction in such patients, so as to provide new ideas for preventing and improving the postoperative cognitive dysfunction in elderly patients in the future.

Varenicline modulates autophagy through PKR/STAT3 pathway to improve postoperative cognitive dysfunction / 中国药理学通报

Aim To evaluate whether varenicline could regulate autophagy through PKR/STAT3 pathway to improve postoperative cognitive dysfunction. Methods Forty healthy male C57BL/6J mice, aged 18 months and weighing (27. 5 ± 2. 5) g, were randomly divided into four groups (n = 10) j control group (CON group), laparotomy group (LAP group), laparotomy with varenicline administration group (Var + LAP group) and varenicline group (Var group). The mice in Var + LAP group and Var group were treated with varenicline (1 mg kg"1 d"1) one day before operation and lasted until 13th day after operation. The other two groups were treated with equal amount of normal saline instead of varenicline. The model of postoperative cognitive dysfunction was established by laparotomy under sevofiurane anesthesia. The novel object recognition task was performed on 10th ~ 12th day after laparotomy, and the Y-maze test was performed on 14th day after laparotomy to detect the cognitive function of the mice. The expression levels of AT8 and LC3B in hippocampus were detected by Western blot and immunofluorescence staining. The expression levels of p-PKR and p-STAT3 were detected by Western blot, and the interaction between STAT3 and PKR was detected by double labeled immunofluorescence staining. Results Compared with CON group, the error numbers and the latency in LAP group increased, the discrimination index decreased, accompanied with the increased expression levels of AT8 and p-PKR, the decreased expression levels of LC3 B and p-STAT3, and the increased interaction of STAT3 and PKR. Compared with LAP group, the error numbers and the latency in Var + LAP group decreased, and the discrimination index increased, associated with the decreased expression of AT8 and p-PKR, the increased expression of LC3B and p-STAT3, and the decreased interaction of STAT3 and PKR. Conclusions Vareni-cline regulates autophagy and eliminates hyperphospho-rylated tau through PKR/STAT3 pathway to improve postoperative cognitive dysfunction.

Characterization of quantitative EEG in patients with postoperative cognitive dysfunction / 医学研究生学报

Objective Very few studies have been reported on the application of quantitative electroencephalogram (qEEG) in patients with postoperative cognitive dysfunction (POCD). This study was to investigate the qEEG features of POCD and provide some help for the early detection and diagnosis of the condition. Methods We enrolled 31 postoperative patients treated in our Department of Critical Care Medicine from January 2018 to October 2018. Based on the pre- and post-operative scores on the Mini-Mental State Examination (MMSE), we divided the patients into a POCD (MMSE score >2, n = 11) and a non-POCD control group (MMSE score ≤2, n = 20). Using the brain function instrument, the electrode set according to the standard international 10-20 system and with bipolar longitudinal F3-P3 and F4-P4 four channels, we conducted bedside monitoring for all the patients and calculated the average value of the consecutive clips of 10-min qEEG. Then, we analyzed the amplitude-integrated EEG (aEEG), relative frequency band energy, relative α variability and spectrum entropy, and the correlation of relative frequency band energy and relative α variability with the MMSE scores. Results Compared with the non-POCD controls, the POCD patients showed significant decreases in the total MMSE scores (28.35 ± 1.27 vs 18.91 ± 2.34, P < 0.05), orientation score (9.75 ± 0.44 vs 6.82 ± 1.47, P < 0.05) and memory score (2.90 ± 0.31 vs 2.09 ± 1.04, P < 0.05) as well as in the concentration, calculation, recalling and language scores (all P < 0.05); and the POCD patients also exhibited marked reduction in the left α variability ([22.59 ± 10.98]% vs [14.39 ± 8.25]%, P < 0.05), right α variability ([24.07 ± 9.73]% vs [15.70 ± 9.59]%, P < 0.05), left α frequency band energy ([7.17 ± 4.73] vs [3.83 ± 2.62] μV2, P < 0.05) and right α frequency band energy ([6.94 ± 4.53] vs [3.82 ± 2.51] μV2, P < 0.05). The MMSE scores were found to be negatively correlated with left α variability (r = -0.793, P = 0.004), right α variability (r = -0.835, P = 0.001), left α frequency band energy (r = -0.633, P = 0.037) and right α frequency band energy (r = -0.682, P = 0.021). Conclusion Quantitative EEG of POCD patients is characterized by significantly decreased α variability and α frequency band energy, which may contribute to the early detection and diagnosis of POCD.

Research progress of the role of postoperative pain in the development of postoperative cognitive dysfunction in geriatric patients / 南方医科大学学报

Previous studies have shown that postoperative cognitive dysfunction (POCD) is related to multiple factors including age, postoperative trauma, inflammation, postoperative pain, and anesthesia, among which postoperative pain is thought to play an important role in the development of POCD. This review summarizes the recent findings in the study of the role of postoperative pain in the pathogenesis of POCD in light of nerve injuries, neural remodeling and stress, and the progress in the prevention and treatment of POCD in elderly patients. It is of vital important to assess the postoperative pain and formulate adequate analgesic regimens for effective prevention and management of POCD to protect the brain functions of elderly patients.