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.
Anesthesia, General ; Humans ; Microglia ; Postoperative Cognitive Complications ; Postoperative Complications

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.
Aged ; Cognitive Dysfunction ; etiology ; Humans ; Inflammation ; Pain, Postoperative ; complications ; therapy ; Postoperative Complications

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.
Animals ; Electroacupuncture ; Hippocampus ; Male ; Memory ; Mice ; Oxidative Stress ; Postoperative Cognitive Complications

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.
Aged ; Aged, 80 and over ; Bradycardia ; Cognitive Dysfunction/prevention & control* ; Delirium/prevention & control* ; Dexmedetomidine/therapeutic use* ; Humans ; Hypotension/drug therapy* ; Interleukin-10 ; Middle Aged ; Postoperative Cognitive Complications/prevention & control* ; Postoperative Complications/epidemiology* ; Prospective Studies ; Tumor Necrosis Factor-alpha

Aged ; Aged, 80 and over ; Analgesics, Opioid ; adverse effects ; Benzodiazepines ; adverse effects ; Cognitive Dysfunction ; chemically induced ; mortality ; Female ; Humans ; Male ; Postoperative Complications ; Randomized Controlled Trials as Topic ; Risk Factors

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. METHODS: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. RESULTS: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ = 6.342 and 13.603, P = 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ = 0.016 and 0.382, P = 0.899 and 0.536). CONCLUSION Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.
Aged ; Cognitive Dysfunction ; epidemiology ; Dexmedetomidine ; pharmacology ; Female ; Humans ; Hypnotics and Sedatives ; pharmacology ; Male ; Midazolam ; pharmacology ; Middle Aged ; Neuropsychological Tests ; Postoperative Complications ; epidemiology ; Propofol ; pharmacology ; Prospective Studies

To observe the impacts of continuous lumbar plexus block (CLPB) on postoperative cognitive dysfunction (POCD) in elderly patients undergoing hip arthroplasty.
 Methods: Sixty elderly patients scheduled for hip arthroplasty with general anesthesia, were randomly allocated into a CLPB group and a PCIA group (n=30 each). In the CLPB group, lumbar plexus block was performed before trachea intubation, and CLPB was used for postoperative analgesia. In the PCIA group, intravenous analgesia was controlled in patients after operation. Visual Analogue Scale (VAS) at 12, 24, and 48 h after operation was recorded. Mini-Mental State Examination (MMSE) scale was used to evaluate the cognitive dysfunction at the 1st day before operation (D0) and at the 1st (D1), 3rd (D3), and 7th (D7) days after operation and the occurrence of POCD was recorded. S-100β concentrations were detected by ELISA at D1, D3, and D7. Postoperative adverse events were recorded.
 Results: VAS scores at 12, 24, and 48 h after operation in the CLPB group were significantly lower than those in the PCIA group (P<0.05). Compared with the PCIA group, the MMSE scores were significantly higher (P<0.05), and the incidence of POCD at D1 and D3 was obviously reduced in the CLPB group (P<0.05). S-100β concentration at D1 and D3 in the CLPB group was significantly lower than that in the PCIA group (P<0.05).
 Conclusion: Application of CLPB in elderly patients undergoing hip arthroplasty could obviously relieve their postoperative pain, inhibit the production of S-100β, and reduce the incidence of early postoperative cognitive dysfunction.
Aged ; Analgesics ; administration & dosage ; Arthroplasty, Replacement, Hip ; adverse effects ; Cognitive Dysfunction ; prevention & control ; Humans ; Incidence ; Lumbosacral Plexus ; Nerve Block ; methods ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Postoperative Complications ; prevention & control

To investigate the effect of N-acetylcysteine(NAC)on cognitive function and nuclear factor erythroid 2 related factor 2/ heme oxygenase-1(Nrf2/HO-1)pathway in mouse models of postoperative cognitive dysfunction. Methods Fifty-four male C57BL/6J mice(3-4 months old)were randomly divided into control group,surgery group,and surgery+NAC group by block randomization.The intramedullary fixation for left tibial fracture surgery was performed to establish postoperative cognitive dysfunction models.NAC(150 mg/kg)was administered intraperitoneally in group surgery+NAC 30 minutes before and 3 hours,6 hours after surgery,while saline was given in control group and surgery group.Six mice in each group were selected randomly underwent Morris water maze test on the third day after surgery.Animals were sacrificed at the first and third postoperative days,and the hippocampus was harvested.Enzyme-linked immunosorbent assay was used to quantify the levels of interleukin-6(IL-6)and malondialdehyde(MDA)in hippocampus.Western blot and real-time polymerase chain reaction were used to measure the expressions of Nrf2 and HO-1 in hippocampus. Results There was no significant difference in swimming speed among three groups(=2.135,=0.114).Compared with control group and surgery+NAC group,the surgery group had prolonged escape latency(<0.01),reduced platform crossing times(<0.01),and shortened time spent in the target quadrant(<0.01).Compared with the control group,the surgery group and the surgery+NAC group had significantly increased levels of IL-6 and MDA in hippocampus at the first postoperative day(all =0.000).On the third postoperative day,there was no significant difference in the levels of IL-6(=0.251)and MDA(=0.103)between control group and surgery+NAC group.The protein expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group(all =0.000).The mRNA expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group (all =0.000). Conclusions NAC pretreatment may reduce oxidative stress and inflammatory response in hippocampus and improve cognitive function.Such effect may be relate to the activation of Nrf2/HO-1 pathway.
Acetylcysteine ; pharmacology ; Animals ; Cognition ; drug effects ; Cognitive Dysfunction ; drug therapy ; etiology ; Heme Oxygenase-1 ; metabolism ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; metabolism ; Postoperative Complications ; Random Allocation

OBJECTIVE: To explore the effect of general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia on the incidence of the post-operative cognitive dysfunction (POCD) in elderly patients.
 METHODS: A total of 100 elderly patients with gastric cancer, who underwent radical gastrectomy in Yan'an People's Hospital from March 2012 to March 2015, were randomly divided into 3 groups: a general anesthesia and patient-controlled intravenous analgesia (PCIA) (Group I, n=35), a general anesthesia combined with epidural anesthesia and PCIA (Group II, n=30), and a general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia (PCEA) (Group III, n=35). There was no significant difference in age, gender, body mass index (BMI), length of operation, American Society of Anesthesiologists (ASA) grade and Mini-Mental State Examination (MMSE) score (all P>0.05). The cognitive function was assessed at the 1st day before operation and at the 6 h, 12 h, 2 d and 6 d after operation by the Mini-Mental State Examination test (MMSE), and the incidence of POCD was compared among the 3 groups. The mean arterial pressure (MAP), blood glucose, cortisol and tumor necrosis factor α (TNF-α) content during the operation were considered. The dosage of sevoflurane (SEVO) in the operation process and the pain score at the 6, 12 and 24 h after operation were recorded.
 RESULTS: The incidence of POCD at 6 h was 45.71% in the Group I and 34.28% in the Group II, which were higher than that in the Group III (10.00%). The incidence of POCD at 12 h was 34.29% in the Group I and 28.57% in the Group II, which were higher than that in the Group III (3.33%). The incidence of POCD at the 2 d was 28.57% in the Group I and 17.14% in the Group II, which were higher than that in the Group III (0). The incidence of POCD at 6 d was 17.14% in the Group I and 2.85% in the Group II, which were higher than that in the Group III (0). The blood glucose, cortisol and TNF-α content were consistent with the incidence of POCD, with significant difference (all P<0.05). The amplitude of MAP in the Group II and the Group III was significantly less than that in the Group I, and the postoperative analgesia effect in the Group III was obviously better than that in the other two groups (both P<0.05).
 CONCLUSION The general anesthesia combined with epidural anesthesia and patient-controlled epidural analgesia can effectively maintain the stable hemodynamic status in the patients and display inhibitory effect on postoperative cognitive dysfunction.
Analgesia, Epidural ; Analgesia, Patient-Controlled ; Anesthesia, Epidural ; Anesthesia, General ; Cognition ; Cognition Disorders ; Cognitive Dysfunction ; Gastrectomy ; Humans ; Incidence ; Methyl Ethers ; Neuropsychological Tests ; Postoperative Complications ; Sevoflurane ; Stomach Neoplasms ; Tumor Necrosis Factor-alpha

OBJECTIVEAnesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.

METHODSFive-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.

RESULTSHere we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.

CONCLUSIONThese results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Anesthetics, Inhalation ; adverse effects ; Animals ; Cognition ; Cognitive Dysfunction ; etiology ; prevention & control ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; drug effects ; Inflammation ; etiology ; prevention & control ; Isoflurane ; adverse effects ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Postoperative Complications ; etiology ; prevention & control ; Random Allocation ; Surgical Procedures, Operative ; adverse effects ; Synapses ; metabolism