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Peripheral surgery-induced neural inflammation is a key pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the mechanism underlying neuroinflammation and associated neural injury remains elusive. Surgery itself can lead to gut damage, and the occurrence of POCD is accompanied by high levels of TNF-α in the serum and blood‒brain barrier (BBB) damage. Reductions in stress, inflammation and protein loss have been emphasized as strategies for enhanced recovery after surgery (ERAS). We designed an amino acids and dipeptide (AAD) formula for injection that could provide intestinal protection during surgery. Through the intraoperative infusion of AAD based on the ERAS concept, we aimed to explore the effect of AAD injection on POCD and its underlying mechanism from the gut to the brain. Here, we observed that AAD injection ameliorated neural injury in POCD, in addition to restoring the function of the intestinal barrier and BBB. We also found that TNF-α levels decreased in the ileum, blood and hippocampus. Intestinal barrier protectors and TNF-α inhibitors also alleviated neural damage. AAD injection treatment decreased HMGB1 production, pyroptosis, and M1 microglial polarization and increased M2 polarization. In vitro, AAD injection protected the impaired gut barrier and decreased TNF-α production, alleviating damage to the BBB by stimulating cytokine transport in the body. HMGB1 and Caspase-1 inhibitors decreased pyroptosis and M1 microglial polarization and increased M2 polarization to protect TNF-α-stimulated microglia in vitro. Collectively, these findings suggest that the gut barrier–TNF-α–BBB–HMGB1–Caspase-1 inflammasome–pyroptosis–M1 microglia pathway is a novel mechanism of POCD related to the gut–brain axis and that intraoperative AAD infusion is a potential treatment for POCD. According to our findings, AAD injection, which is based on the ERAS concept, alleviates POCD by decreasing the activity of the gut barrier–TNF‐α–BBB–HMGB1–Caspase-1 inflammasome–pyroptosis–M1 microglial axis [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of the microRNA (miRNA)‐669f‐5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice. Methods: Sixty‐six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air‐treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation. Results: The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR‐669f‐5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR‐669f‐5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR‐669f‐5p/Dctd and the toll‐like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR‐669f‐5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR‐669f‐5p could reduce the expression of the Dctd gene by binding to its 3′untranslated region. Conclusion: The miR‐669f‐5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction, a common neurological complication in the perioperative period, seriously affects patient survival and prognosis. Its high incidence has made the study of postoperative cognitive dysfunction challenging. Whether the clinical application of dexmedetomidine, a potential neuroprotective drug, can reduce the incidence of postoperative cognitive dysfunction is controversial, although several potential mechanisms by which dexmedetomidine improves postoperative cognitive dysfunction have been identified; therefore, this remains an area in need of further exploration. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a frequent neurological complication encountered during the perioperative period with unclear mechanisms and no effective treatments. Recent research into the pathogenesis of POCD has primarily focused on neuroinflammation, oxidative stress, changes in neural synaptic plasticity and neurotransmitter imbalances. Given the high-energy metabolism of neurons and their critical dependency on mitochondria, mitochondrial dysfunction directly affects neuronal function. Additionally, as the primary organelles generating reactive oxygen species, mitochondria are closely linked to the pathological processes of neuroinflammation. Surgery and anesthesia can induce mitochondrial dysfunction, increase mitochondrial oxidative stress, and disrupt mitochondrial quality-control mechanisms via various pathways, hence serving as key initiators of the POCD pathological process. We conducted a review on the role and potential mechanisms of mitochondria in postoperative cognitive dysfunction by consulting relevant literature from the PubMed and EMBASE databases spanning the past 25 years. Our findings indicate that surgery and anesthesia can inhibit mitochondrial respiration, thereby reducing ATP production, decreasing mitochondrial membrane potential, promoting mitochondrial fission, inducing mitochondrial calcium buffering abnormalities and iron accumulation, inhibiting mitophagy, and increasing mitochondrial oxidative stress. Mitochondrial dysfunction and damage can ultimately lead to impaired neuronal function, abnormal synaptic transmission, impaired synthesis and release of neurotransmitters, and even neuronal death, resulting in cognitive dysfunction. Targeted mitochondrial therapies have shown positive outcomes, holding promise as a novel treatment for POCD. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery. Methods: One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb. Discussion: The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD. Trial registration: The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

Purpose of Review: To provide up to date information on postoperative delirium and neurocognitive disorders in surgical cancer patients. Recent Findings: Established risk factors such as age, psychosocial factors, comorbidities, frailty and preexisting cognitive decline continue to exhibit associations with perioperative neurocognitive disorders (PND); novel risk factors identified recently include microbiome composition and vitamin D deficiency. Prevention measures include cognitive prehabilitation, perioperative geriatric assessment and multidisciplinary care, dexmedetomidine and multimodal analgesic techniques. Studies investigating ciprofol, remimazolam, esketamine, ramelteon and suvorexant have shown encouraging results. Controversy remains regarding the use of inhalational versus intravenous general anesthesia. Summary: Innovative approaches to address PND are a rapidly developing area of research, but more studies are needed to identify effective prevention and management interventions. Despite challenges and controversy in the field, implementation of best practice can reduce the detrimental impact of PND on patients, caregivers, and society at large. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as a potential etiology for postoperative cognitive dysfunction (POCD). Myocyte‐specific enhancer factor 2C (MEF2C), a transcription factor expressed in various brain cell types, has been implicated in cognitive disorders. This study sought to ascertain whether MEF2C governs postoperative cognitive capacity by affecting ferroptosis. Methods: Transcriptomic analysis of public data was used to identify MEF2C as a candidate differentially expressed gene in the hippocampus of POCD mice. The POCD mouse model was established via aseptic laparotomy under isoflurane anesthesia after treatment with recombinant adeno‐associated virus 9 (AAV9)‐mediated overexpression of MEF2C and/or the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Cognitive performance, Nissl staining, and ferroptosis‐related parameters were assessed. Dual‐luciferase reporter gene assays and chromatin immunoprecipitation assays were implemented to elucidate the mechanism by which MEF2C transcriptionally activates GPX4. Results: MEF2C mRNA and protein levels decreased in the mouse hippocampus following anesthesia and surgery. MEF2C overexpression ameliorated postoperative memory decline, hindered lipid peroxidation and iron accumulation, and enhanced antioxidant capacity, which were reversed by RSL3. Additionally, MEF2C was found to directly bind to the Gpx4 promoter and activate its transcription. Conclusions: Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD. Methods: Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1. Results: Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus. Conclusions: Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD. [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT‐1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT‐1 expression. Methods: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT‐1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long‐term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT‐1 in GFAP‐Cre mice. Besides, AAV‐Camkllα‐hM4Di‐mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. Results: Our study found T2DM but not A/S reduced GLT‐1 expression in hippocampal astrocytes. Interestingly, GLT‐1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT‐1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT‐1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. Conclusions: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT‐1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Materials and Methods: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Results: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. Conclusions: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients. [ABSTRACT FROM AUTHOR]

Thalamus function and structure are known predictors of individual differences in the risk of age-related neurocognitive disorders (NCD), such as dementia. However, to date, little is known about their role in the perioperative setting. Here, we provide a narrative review of brain-imaging studies of preoperative and postoperative thalamus scanning parameters associated with risks of developing perioperative NCD, such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) during the postoperative phase. These findings are discussed in light of the concept of reserve capacity. [ABSTRACT FROM AUTHOR]

Background: Perioperative neurocognitive disorders are often neglected and undiagnosed. There are known risk factors for these disorders (e.g., higher levels of frailty, cognitive decline before surgery). However, these factors are usually not assessed in the daily clinical setting. One of the main reasons for this lack of examination is the absence of a suitable cognitive function test that can be used in acute clinical settings. The primary aim of this study was to determine correlations between preoperative and postoperative scores on three cognitive tests (the Mini Mental State Exam (MMSE), the Clock Drawing Test (CDT) and the Test of Gestures (TEGEST). Methods: This was a prospective, monocentric, observational study that included one cohort of patients aged 65 years and older. Patients underwent acute or elective surgical operations. Preanaesthesia tests were administered. After the operation, the patients completed the same tests between the 2nd postoperative day and discharge. Preoperative and postoperative cognitive test scores were assessed. Results: This study included 164 patients. The arithmetic mean age was 74.5 years. The strongest correlations were observed between MMSE scores and TEGEST scores (r = 0.830 before and 0.786 after surgery, P < 0.001). To compare the MMSE and the TEGEST, the MMSE was divided into 2 categories—normal and impaired—and good agreement was found among 76.2% of the participants (ϰ = 0.515). If the TEGEST scoring system was changed so that scores of 4–6 indicated normal cognition and scores of 0–3 indicated cognitive impairment, the level of agreement would be 90.8%, ϰ = 0.817. Only 5.5% of the patients had impaired MMSE scores and normal TEGEST scores, whereas 3.7% of the respondents normal MMSE scores and impaired TEGEST scores. Conclusion: According to our results, the TEGEST is a suitable option for assessing cognitive functioning before surgery among patients who are at risk of developing perioperative neurocognitive disorders. This study revealed that it is necessary to change the rating scale for the TEGEST so that scores of 4–6 indicate normal cognition and scores of 0–3 indicate cognitive impairment. In clinical practice, the use of the TEGEST may help to identify patients at risk of perioperative neurocognitive disorders. [ABSTRACT FROM AUTHOR]

Background Postoperative cognitive dysfunction (POCD) is a generally recognized complication experienced by patients who receive anesthesia during surgery. Sevoflurane, the most commonly used inhaled anesthetic, has been shown to trigger neuroinflammation that promotes to POCD. Objective This study examined the pathological mechanism by which sevoflurane causes neuroinflammation, participating in POCD. Methods To establish a neurocyte injury model, the human neuroblastoma cell lines SH-SY5Y and SK-N-SH were treated with sevoflurane. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays. The reactive oxygen species (ROS) level was evaluated by DCFH-DA assays. A lactate dehydrogenase (LDH) Cytotoxicity Assay Kit was used to measure LDH levels. Inflammatory cytokine levels were measured using enzyme-linked immunosorbent assay assays. Gene expression densities and protein abundance were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. The interaction between YTHDF1 and dual specific phosphatase 6 (DUSP6) was validated using RNA immunoprecipitation (RIP)-qPCR and methylated RIP (MeRIP)-qPCR assays. Flow cytometry was performed to determine apoptosis. Results Sevoflurane promoted apoptosis, oxidative stress, and neuroinflammation and repressed the expression levels of YTHDF1 and DUSP6. Furthermore, YTHDF1 overexpression reversed sevoflurane-induced neuroinflammation in neurocytes. DUSP6 overexpression could alleviate the neuroinflammation induced by sevoflurane via regulating the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Moreover, YTHDF1 enhanced DUSP6 expression. Conclusion Sevoflurane-stimulated neuroinflammation by regulating DUSP6 via YTHDF1. Sevoflurane promoted neuroinflammation by regulating DUSP6 via YTHDF1 in an in vitro model of POCD. [ABSTRACT FROM AUTHOR]

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period. Using a repeated neonatal ISO exposure-induced PND rat model, we investigated the effects of methylene blue (MB) pretreatment on repeated neonatal isoflurane exposure-induced brain injury and memory loss. Intraperitoneal injection of low-dose MB (1 mg/kg) was conducted three times 24 h before each ISO exposure. The Barnes maze and novel objection test were conducted to assess learning and memory. Immunofluorescence staining, F-Jade C staining, TUNEL staining, and Western blot analysis were performed to determine mitochondrial fragmentation, neuronal injury, degeneration, and apoptosis. Evans blue extravasation assay, total antioxidant capacity assay, MDA assay kit, and related inflammatory assay kits were used to test blood–brain barrier (BBB) disruption, antioxidant capacity, and neuroinflammation. Behavioral tests revealed that MB pretreatment significantly ameliorated ISO exposure-induced cognitive deficits. In addition, MB pretreatment alleviates neuronal injury, apoptosis, and degeneration. Furthermore, the BBB integrity was preserved by MB pretreatment. Additional studies revealed that ISO-induced excessive mitochondrial fragmentation, oxidative stress, and neuroinflammation were significantly attenuated by MB pretreatment in the PND rat model. Our findings suggest that MB pretreatment alleviates ISO exposure-induced brain injury and memory loss for the first time, supporting MB pretreatment as a promising approach to protect the brain against neonatal ISO exposure-induced postoperative cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Postoperative depression (POD) and postoperative cognitive dysfunction (POCD) have placed heavy burden on patients' physical and mental health in recent years. Sleep disturbance before surgery is a common phenomenon that has been increasingly believed to affect patients' recovery, especially in aged patients, while little attention has been paid to sleep disruption before surgery and the potential mechanism remains ambiguous. Ketamine has been reported to attenuate POCD after cardiac surgery and elicit rapid-acting and sustained antidepressant actions. The present study aimed to clarify the effect of esketamine's (the S-enantiomer of ketamine) protective effects and possible mechanisms of action in POCD and POD. Our results showed that sleep disturbance before surgery exacerbated microglial M1 polarization and microglial BDNF-TrkB signalling dysfunction induced by surgery, resulting in postoperative emotional changes and cognitive impairments. Notably, treatment with esketamine reversed the behavioural abnormalities through inhibiting the M1 polarization of microglia and the inflammatory response thus improving BDNF-TrkB signalling in vivo and vitro. In addition, esketamine administration also reversed the impaired hippocampal synaptic plasticity which has been perturbed by sleep disturbance and surgery. These findings warrant further investigations into the interplay of esketamine and may provide novel ideas for the implication of preoperative preparations and the prevention of postoperative brain-related complications. [ABSTRACT FROM AUTHOR]

Aims: Postoperative cognitive dysfunction (POCD) is prevalent among the elderly, characterized primarily by cognitive decline after surgery. This study aims to explore how extracellular vesicles (EVs) derived from BV2 microglial cells, with and without the C‐C chemokine receptor type 5 (CCR5), affect neuroinflammation, neuronal integrity, and cognitive function in a POCD mouse model. Methods: We collected EVs from LPS‐stimulated BV2 cells expressing CCR5 (EVsM1) and from BV2 cells with CCR5 knockdown (EVsM1‐CCR5). These were administered to POCD‐induced mice. Protein interactions between CCR5, G‐protein‐coupled receptors (GPCRs), and Ras were analyzed using structure‐based docking and co‐immunoprecipitation (Co‐IP). We assessed the phosphorylation of p38 and Erk, the expression of synaptic proteins PSD95 and MAP2, and conducted Morris Water Maze tests to evaluate cognitive function. Results: Structure‐based docking and Co‐IP confirmed interactions between CCR5, GPR, and Ras, suggesting a CCR5‐GPCRs‐Ras‐MAPK pathway involvement in neuroinflammation. EVsM1 heightened neuroinflammation, reduced synaptic integrity, and impaired cognitive function in POCD mice. In contrast, EVsM1‐CCR5 reduced neuroinflammatory markers, preserved synaptic proteins, enhanced dendritic spine structure, and improved cognitive outcomes. Conclusion: EVsM1 induced neuroinflammation via the CCR5‐GPCRs‐Ras‐MAPK pathway, with EVsM1‐CCR5 showing protective effects on POCD progression, suggesting a new therapeutic strategy for POCD management via targeted modification of microglial EVs. [ABSTRACT FROM AUTHOR]

Background: Mini-mental State Examination (MMSE) is widely accepted clinically for postoperative cognitive dysfunction (POCD) assessment. This study aims to investigate the post-operative cognitive changes among high-risk cardiothoracic patients and establish a standardised approach to post-surgery cognitive assessment. Methods: This is a prospective cohort study, where cognitive assessments were done 1-day before surgery, at discharge, and during 6 weeks of follow-up. Sample size calculation, accounting for an estimated 20% dropout rate, determined a minimum of 170 subjects were required for the study. Reduction of MMSE score of more than 2.5 was considered as having POCD. Score differences between groups were analysed using T-test and analysis of variance (ANOVA), while consistency between tools was analysed using correlation and regression. Results: A total of 188 patients completed the study, with a POCD prevalence of 20.2% and 6.9% at discharge and at the 6 week follow up, respectively. All cognitive tools show a significant difference between preoperative and postoperative scores. All tests show a significant moderate correlation with MMSE. Conclusions: In conclusion, it is imperative to employ a battery of cognitive assessments to evaluate cognitive changes comprehensively. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) occurs after surgery and severely impairs patients' quality of life. Finding POCD-associated variables can aid in its diagnosis and prognostication. POCD is associated with noncoding RNAs, such as microRNAs (miRNAs), involved in metabolic function, immune response alteration, and cognitive ability impairment; however, the underlying mechanisms remain unclear. The aim of this study was to investigate hub miRNAs (i.e., miRNAs that have an important regulatory role in diseases) regulating postoperative cognitive function and the associated mechanisms. Hub miRNAs were identified by bioinformatics, and their expression in mouse hippocampus tissues was determined using real-time quantitative polymerase chain reaction. Hub miRNAs were overexpressed or knocked down in cell and animal models to test their effects on neuroinflammation and postoperative cognitive function. Six differentially expressed hub miRNAs were identified. miR-206-3p was the only broadly conserved miRNA, and it was used in follow-up studies and animal experiments. Its inhibitors reduced the release of proinflammatory cytokines in BV-2 microglia by regulating its target gene, brain-derived neurotrophic factor (BDNF), and the downstream signaling pathways. miR-206-3p inhibition suppressed microglial activation in the hippocampi of mice and improved learning and cognitive decline. Therefore, miR-206-3p significantly affects POCD, implying its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

As the population ages, the number of patients with postoperative cognitive dysfunction increases. This study aims to investigate the mechanisms of Shenmai injection as a therapeutic strategy for postoperative cognitive dysfunction using a network pharmacology approach. Shenmai injection and its targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Postoperative cognitive dysfunction-associated protein targets were identified using the GeneCards and DisGeNET databases. Subsequently, a protein-protein interaction network was constructed using the String database. For treating postoperative cognitive dysfunction, the core targets of Shenmai injection were identified through topological analysis, followed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed for annotation. Molecular docking was performed on the screened core targets and components. One hundred and eighty-two related targets of Shenmai injection in treating postoperative cognitive dysfunction were identified. Eleven active ingredients in Shenmai injection were detected to have a close connection with postoperative cognitive dysfunction-related targets. Additionally, Gene Ontology analysis revealed 10 biological processes, 10 cellular components and 10 molecular functions. The Kyoto Encyclopedia of Genes and Genomes analysis identified 20 signaling pathways. The docking results indicated five active ingredients from Shenmai injection can fit in the binding pockets of all three candidate targets. Thus, the present work systematically explored the anti-postoperative cognitive dysfunction mechanism of potential targets and signaling pathways of Shenmai injection. These results provide an important reference for subsequent basic research on postoperative cognitive dysfunction. [ABSTRACT FROM AUTHOR]

An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients. [ABSTRACT FROM AUTHOR]

Perioperative neurocognitive disorders (PNDs) are now considered the most common neurological complication in older adult patients undergoing surgical procedures. A significant increase exists in the incidence of post-operative disability and mortality in patients with PNDs. However, no specific treatment is still available for PNDs. Recent studies have shown that exercise may improve cognitive dysfunction-related disorders, including PNDs. Neuroinflammation is a key mechanism underlying exercise-induced neuroprotection in PNDs; others include the regulation of gut microbiota and mitochondrial and synaptic function. Maintaining optimal skeletal muscle mass through preoperative exercise is important to prevent the occurrence of PNDs. This review summarizes current clinical and preclinical evidence and proposes potential molecular mechanisms by which perioperative exercise improves PNDs, providing a new direction for exploring exercise-mediated neuroprotective effects on PNDs. In addition, it intends to provide new strategies for the prevention and treatment of PNDs. [ABSTRACT FROM AUTHOR]

Background Postoperative cognitive dysfunction (POCD) manifests as a subtle decline in cognition, potentially leading to unfavourable postoperative outcomes. We explored the impact of POCD on physical function, length of hospital stay (LOS), dementia and mortality outcomes. Methods PubMed and Scopus were searched until May 2023. All studies of major surgical patients that assessed POCD and outcomes of interest were included. POCD effects were stratified by surgery type (cardiac and noncardiac) and time of POCD assessment (<30 and ≥30 days postsurgery). Results Of 2316 studies, 20 met the inclusion criteria. POCD was not associated with functional decline postsurgery. Patients who experienced POCD postcardiac surgery had an increased relative risk (RR) of death of 2.04 [(95% CI: 1.18, 3.50); I 2 = 0.00%]. Sensitivity analyses showed associations with intermediate-term mortality among noncardiac surgical patients, with an RR of 1.84 [(95% CI: 1.26, 2.71); I 2 = 0.00%]. Patients who developed POCD <30 days postcardiac and noncardiac surgeries experienced longer LOS than those who did not [mean difference (MD) = 1.37 days (95% CI: 0.35, 2.39); I 2 = 92.38% and MD = 1.94 days (95% CI: 0.48, 3.40); I 2 = 83.29%, respectively]. Postoperative delirium (POD) may contribute to the heterogeneity observed, but limited data were reported within the studies included. Conclusions Patients undergoing cardiac and noncardiac surgeries who developed POCD <30 days postsurgery had poorer outcomes and an increased risk of premature death. Early recognition of perioperative neurocognitive disorders in at-risk patients may enable early intervention. However, POD may confound our findings, with further studies necessary to disentangle the effects of POD from POCD on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Postoperative Cognitive Dysfunction (POCD) is a complication that arises in the elderly. Because of the limited knowledge of POCD, researchers must handle a substantial amount of data to ensure the comprehensive collection of all relevant factors. To deal with this data, a validation study is a valuable method that aids in qualifying the data. Materials and Methods: A validation exercise was performed for 40% of the data in the Siriraj POCD database (n=250) in 2020-2023. The validation covered 30 items, including demographic data, surgical and anesthetic factors. The validation study had two components: internal validation, which aimed to assess the completeness, uniformity, plausibility, and accuracy of the data in the database, and external validation, where the results were compared to external literature to confirm their correspondence. Results: The completeness was 99.2% for creatinine and 94.0% for hemoglobin, while others showed 100% completeness. The accuracy ranged from 73.6% to 99.6%, with a median of 97.4%. Most errors found were related to "body weight", followed by "hemoglobin levels" and "Propofol targeted controlled infusion", with accuracy rates of 73.6%, 84.0%, and 85.2%, respectively. In the external validation, the POCD incidence at 1 week from surgery in the literature review ranged from 8.9%-46.1% compared to 26.0% in our study. Conclusion: The Siriraj POCD cohort study database was found to be reasonably valid. Therefore, this data can support high-quality research. Our recommendations for developing a good database include implementing a dedicated plan, employing trained staff, and using reliable data sources. [ABSTRACT FROM AUTHOR]

Peri-operative neurocognitive disorders (PNDs) include postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Children and the elderly are the two populations most vulnerable to the development of POD and POCD, which results in both high morbidity and mortality. There are many factors, including neuroinflammation and oxidative stress, that are associated with POD and POCD. General anesthesia is a major risk factor of PNDs. However, the molecular mechanisms of PNDs are poorly understood. Dexmedetomidine (DEX) is a useful sedative agent with analgesic properties, which significantly improves POCD in elderly patients. In this review, the current understanding of anesthesia in PNDs and the protective effects of DEX are summarized, and the underlying mechanisms are further discussed. [ABSTRACT FROM AUTHOR]

Objective: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. Methods: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. Results: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). Conclusion: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane. [ABSTRACT FROM AUTHOR]

Background: Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD. Methods: In this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat. Discussion: This trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients. Trial registration: The study protocol was prospectively registered at the Clinical trials (https://clinicaltrials.gov, NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a common complication affecting elderly patients after anaesthesia. It is characterised by acute or persistent impairments of attention, learning and memory after surgery. This cognitive disorder can lead not only to an increase in postoperative complications and prolonged hospital stays, but also to an increased societal burden and waste of medical resources. Stellate ganglion block (SGB) is a commonly used nerve block technique in clinical practice. It works to block neural signals from stellate ganglion to control pain or treat certain conditions primarily by injecting local anaesthetics. This article summarises the mechanisms by which SGB improves POCD, focusing on the regulation of cerebral vasculature, oxidative stress and inflammatory responses. It aims to provide elderly patients with an approach to safer and more effective postoperative recovery and seek new therapies to alleviate the burden of POCD. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) has become the popular critical post-operative consequences, especially cardiopulmonary bypass surgery, leading to an increased risk of mortality. However, no therapeutic effect about POCD. Probiotics are beneficial bacteria living in the gut and help to reduce the risk of POCD. However, the detailed mechanism is still not entirely known. Therefore, our research aims to uncover the effect and mechanism of probiotics in relieving POCD and to figure out the possible relationship between kynurenine metabolic pathway. 36 rats were grouped into three groups: sham operated group (S group, n = 12), Cardiopulmonary bypass group (CPB group, n = 12), and probiotics+CPB (P group, n = 12). After CPB model preparation, water maze test and Garcia score scale was performed to identify the neurological function. Immunofluorescence and Hematoxylin and eosin staining has been used for hippocampal neurons detection. Brain injury related proteins, oxidative stress factors, and inflammatory factors were detected using enzyme-linked immunosorbent assays (ELISA). Neuronal apoptosis was detected by TdT-mediated dUTP nick end-labeling (TUNEL) staining and western blot. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was performed to detect the key factors of the kynurenine metabolic pathway. Our results demonstrated that probiotics improved neurological function of post-CPB rats. The administration of probiotics ameliorated memory and learning in spatial terms CPB rats (P < 0.05). Hematoxylin and eosin (H&E) staining data, S‐100β and neuron-specific enolase (NSE) data convinced that probiotics agonists reduced brain damage in CPB rats (P < 0.05). Moreover, probiotics regulated inflammatory factors, meanwhile attenuated hippocampal neuronal apoptosis. Probiotics alleviated POCD in rats with CPB through regulation of kynurenine metabolic signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effective pain management is vital in critical care settings, particularly post-surgery. Clinicians should maintain objective and efficient standards to assess pain in a patient-centered manner, in order to effectively manage this complex issue. A newer technology, the nociception level (NOL) index, shows promise in achieving this task through its multi-parameter evaluation. METHODS: This study was a prospective, controlled, randomized trial involving two groups of patients (n=30 each) in a diverse intensive care unit. Participants were over 18 years old with American Society of Anesthesiology scores ranging from I to III and were scheduled for critical care follow-up after general anesthesia. All subjects followed a standard analgesia protocol that included rescue analgesia. Drug administration was guided by a numeric rating scale and the critical care pain observation tool in the Control Group, while it was guided by nociception level index monitoring in the NOL Group. RESULTS: Pain scores between the two groups did not significantly differ. However, within the NOL Group, pain scores and nociception values displayed a strong positive correlation. Notably, total analgesic consumption was significantly lower in the NOL Group (p=0.036). CONCLUSION: Monitoring pain using the nociception level index is an effective method for detecting pain compared to standard pain scores utilized in critical care. Its guidance facilitates personalized analgesic titration. Additionally, the potential of nociception level index guidance to reduce the duration of intensive care and hospital stays may be linked to its effects on delirium, a connection that awaits further exploration in future studies. [ABSTRACT FROM AUTHOR]

This study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague–Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra‐high‐performance liquid chromatography–mass spectrometry (UHPLC–MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite‐disease‐target" network; and performs protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K‐Akt pathway, the HIF‐1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD. [ABSTRACT FROM AUTHOR]

The effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity have attracted the attention of neuroscientists. Microglia play important roles in the inflammatory process and in neuromodulation of the central nervous system. Microglia-mediated neuroinflammation is a key mechanism of neurocognitive dysfunction during the perioperative period. Microglial activation by GAAs induces antiinflammatory and pro-inflammatory effects in microglia, suggesting that GAAs play a dual role in the mechanism of postoperative cognitive dysfunction. Understanding of the mechanisms by which GAAs regulate microglia may help to reduce the incidence of postoperative adverse effects. Here, we review the actions of GAAs on microglia and the consequent changes in microglial function. We summarize clinical and animal studies associating microglia with general anesthesia and describe how GAAs interact with neurons via microglia to further explore the mechanisms of action of GAAs in the nervous system. [ABSTRACT FROM AUTHOR]

Background and Aims: Postoperative neurocognitive dysfunction (PNCD) commonly occurs after surgery and prolongs hospital stays. Both direct noxious stimuli to the central nervous system and systemic inflammation have been implicated. Due to their potent anti-inflammatory effects, corticosteroids have been utilised to attenuate the incidence and severity of PNCD. This systematic review and meta-analysis strived to evaluate the prophylactic role of perioperative corticosteroids for PNCD. Methods: A search was run in pre-defined databases for randomised controlled trials (RCTs) assessing the role of corticosteroids in preventing PNCD. The incidence of PNCD within 1 month was the primary outcome. Secondary outcomes included the use of antipsychotic medications for the treatment, postoperative infection, and hospital length of stay. The results are exhibited as odds ratio (OR) and the mean difference (MD) with 95% confidence interval (CI). Results: Fifteen RCTs comprising 15,398 patients were included. The incidence of PNCD was significantly lower in the corticosteroid group than in the control group, with a pooled OR of 0.75 (95% CI 0.58, 0.96; P = 0.02; I2 = 66%). Trial sequential analysis showed the clinical benefit of corticosteroids in preventing PNCD; however, the requisite information size is still inadequate. The sub-group analysis supported the prophylactic effect of corticosteroids on delirium prevention but not on delayed neurocognitive recovery. Conclusions: Our meta-analysis revealed statistically significant protective effects of corticosteroids on the incidence of PNCD. However, further studies are still needed to confirm the protective role of this commonly used and relatively safe strategy for preventing PNCD. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. Methods: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. Results: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. Conclusions: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery. [ABSTRACT FROM AUTHOR]

Delirium is a severe postoperative complication associated with poor overall and especially neurocognitive prognosis. Altered brain mineralization is found in neurodegenerative disorders but has not been studied in postoperative delirium and postoperative cognitive decline. We hypothesized that mineralization‐related hypointensity in susceptibility‐weighted magnetic resonance imaging (SWI) is associated with postoperative delirium and cognitive decline. In an exploratory, hypothesis‐generating study, we analysed a subsample of cognitively healthy patients ≥65 years who underwent SWI before (N = 65) and 3 months after surgery (N = 33). We measured relative SWI intensities in the basal ganglia, hippocampus and posterior basal forebrain cholinergic system (pBFCS). A post hoc analysis of two pBFCS subregions (Ch4, Ch4p) was conducted. Patients were screened for delirium until the seventh postoperative day. Cognitive testing was performed before and 3 months after surgery. Fourteen patients developed delirium. After adjustment for age, sex, preoperative cognition and region volume, only pBFCS hypointensity was associated with delirium (regression coefficient [90% CI]: B = −15.3 [−31.6; −0.8]). After adjustments for surgery duration, age, sex and region volume, perioperative change in relative SWI intensities of the pBFCS was associated with cognitive decline 3 months after surgery at a trend level (B = 6.8 [−0.9; 14.1]), which was probably driven by a stronger association in subregion Ch4p (B = 9.3 [2.3; 16.2]). Brain mineralization, particularly in the cerebral cholinergic system, could be a pathomechanism in postoperative delirium and cognitive decline. Evidence from our studies is limited because of the small sample and a SWI dataset unfit for iron quantification, and the analyses presented here should be considered exploratory. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current nonpharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction is a common complication following anesthesia and surgery, and is associated with oxidative stress and apoptosis in the central nervous system. Resveratrol, an antioxidant, natural polyphenol, has been reported to have neuroprotective effect. The aim of this study was to examine whether resveratrol could attenuate the apoptosis and oxidative stress in a cell model of postoperative cognitive dysfunction. A cell model of postoperative cognitive dysfunction was constructed using human microglial clone 3 cells exposed to 1000 ng/ml lipopolysaccharide, 50 µM resveratrol, and their combination for 48 h. Then, the cell viability, proliferation, apoptosis, production of reactive oxygen species, and the expression of apoptosis-related genes and nuclear factor-E2-related factor 2 and its downstream antioxidant genes were examined. In the postoperative cognitive dysfunction cell model, lipopolysaccharide decreased the cell viability and proliferation, while it increased cell apoptosis and reactive oxygen species level. Lipopolysaccharide also upregulated the expression of pro-apoptotic genes (Bcl-2-associated X-protein and caspase-3) and genes involved in nuclear factor-E2-related factor 2-mediated antioxidant pathway (nuclear factor-E2-related factor 2, Kelch-like ECH-associated protein 1, heme oxygenase-1, and superoxide dismutase-2) in human microglial clone 3 cells. Resveratrol ameliorated the lipopolysaccharide-induced decrease of cell viability and proliferation, increase of cell apoptosis and reactive oxygen species level, and upregulation of the expression of pro-apoptotic genes. Additionally, resveratrol upregulated the expression of nuclear factor-E2-related factor 2 and its downstream antioxidant genes in lipopolysaccharide-treated human microglial clone 3 cells. Resveratrol protects human microglial clone 3 cells against lipopolysaccharide-induced injury by reducing oxidative stress through activating nuclear factor-E2-related factor 2-mediated antioxidant pathway. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Pathophysiology is the property of Jinan University, School of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Postoperative cognitive dysfunction (POCD) is a frequent complication after major surgery and anesthesia exposure, particularly in advanced aging. However, the effects of anesthesia/stereotaxic surgery (A/SS) on cognitive function in rats remain inadequately understood. This study aims to elucidate the effects of A/SS on cognitive function in male Sprague Dawley rats and explore potential alterations in hippocampal synaptic plasticity. Male Sprague Dawley rats, aged 6 months, were subjected to anesthesia (A) or A/SS, involving anesthesia with ketamine/xylazine (50/10 mg/kg, ip) and stereotaxic surgery to create a burr hole above the lateral ventricle. Anxiety-like behavior and locomotor activity were assessed using the open-field test one week post-surgery. Spatial memory and learning were evaluated through the Y-Maze test and novel object recognition test (NORT). Moreover, to determine hippocampal synaptic plasticity, we evaluated hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus synapses. No statistically significant differences in anxiety and motor activity were observed between groups. Compared to the no-treatment group, the A/SS group rats exhibited a significantly (p<0.05) lower exploration of a novel arm and novel object in the Y-Maze and NORT, respectively. Furthermore, on postoperative day 7, LTP induced by high-frequency stimulation in the dentate gyrus region was attenuated (p<0.05) in the A/SS group compared to the no-treatment group. These findings indicated that A/SS induced cognitive decline and functional synaptic plasticity dysfunction. The results of the present study may be useful for future studies examining cognitive functions in experimental models involving such procedures. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Jilin University (Medicine Edition) is the property of Jilin University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Postoperative cognitive dysfunction (POCD) is a common neurological complication of anesthesia and surgery in aging individuals. Neuroinflammation has been identified as a hallmark of POCD. However, safe and effective treatments of POCD are still lacking. Itaconate is an immunoregulatory metabolite derived from the tricarboxylic acid cycle that exerts anti-inflammatory effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we investigated the effects and underlying mechanism of 4-octyl itaconate (OI), a cell-permeable itaconate derivative, on POCD in aged mice. Methods: A POCD animal model was established by performing aseptic laparotomy in 18-month-old male C57BL/6 mice under isoflurane anesthesia while maintaining spontaneous ventilation. OI was intraperitoneally injected into the mice after surgery. Primary microglia and neurons were isolated and treated to lipopolysaccharide (LPS), isoflurane, and OI. Cognitive function, neuroinflammatory responses, as well as levels of gut microbiota and their metabolites were evaluated. To determine the mechanisms underlying the therapeutic effects of OI in POCD, ML385, an antagonist of Nrf2, was administered intraperitoneally. Cognitive function, neuroinflammatory responses, endogenous neurogenesis, neuronal apoptosis, and Nrf2/extracellular signal-related kinases (ERK) signaling pathway were evaluated. Results: Our findings revealed that OI treatment significantly alleviated anesthesia/surgery-induced cognitive impairment, concomitant with reduced levels of the neuroinflammatory cytokines IL-1β and IL-6, as well as suppressed activation of microglia and astrocytes in the hippocampus. Similarly, OI treatment inhibited the expression of IL-1β and IL-6 in LPS and isoflurane-induced primary microglia in vitro. Intraperitoneal administration of OI led to alterations in the gut microbiota and promoted the production of microbiota-derived metabolites associated with neurogenesis. We further confirmed that OI promoted endogenous neurogenesis and inhibited neuronal apoptosis in the hippocampal dentate gyrus of aged mice. Mechanistically, we observed a decrease in Nrf2 expression in hippocampal neurons both in vitro and in vivo, which was reversed by OI treatment. We found that Nrf2 was required for OI treatment to inhibit neuroinflammation in POCD. The enhanced POCD recovery and promotion of neurogenesis triggered by OI exposure were, at least partially, mediated by the activation of the Nrf2/ERK signaling pathway. Conclusions: Our findings demonstrate that OI can attenuate anesthesia/surgery-induced cognitive impairment by stabilizing the gut microbiota and activating Nrf2 signaling to restrict neuroinflammation and promote neurogenesis. Boosting endogenous itaconate or supplementation with exogenous itaconate derivatives may represent novel strategies for the treatment of POCD. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. Methods: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. Main results: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81–2.24, p = 0.25, I2 = 0%). Conclusion: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery. [ABSTRACT FROM AUTHOR]

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative cognitive dysfunction (POCD) is a common neurological issue following cardiopulmonary bypass (CPB)-assisted heart surgery. Remote ischemic preconditioning (RIPC) increases the tolerance of vital organs to ischemia/reperfusion injury, leading to reduced brain injury biomarkers and improved cognitive control. However, the exact mechanisms underlying RIPC's neuroprotective effects remain unclear. This systematic review aimed to explore the hypothesis that RIPC lowers neurocognitive dysfunction in patients undergoing CPB surgery. Method: All relevant studies were searched in PubMed, ScienceDirect, EBSCOhost, Google Scholar, Semantic Scholar, Scopus, and Cochrane Library database. Assessment of study quality was carried out by two independent reviewers individually using the Cochrane Risk of Bias (RoB-2) tool. Meta-analysis was performed using a fixed-effect model due to low heterogeneity among studies, except for those with substantial heterogeneity. Results: A total of five studies with 1,843 participants were included in the meta-analysis. RIPC was not associated with reduced incidence of postoperative cognitive dysfunction (five RCTs, odds ratio [OR: ] 0.79, 95% confidence interval [CI]: 0.56-1.11) nor its improvement (three RCTs, OR: 0.80, 95% CI: 0.50-1.27). In addition, the analysis of the effect of RIPC on specific cognitive function tests found that pooled SMD for RAVLT 1-3 and RAVLT LT were -0.07 (95% CI: -0.25,012) and -0.04 (95% CI: -0.25-0.12), respectively, and for VFT semantic and phonetic were -0.15 (95% CI: -0.33-0.04) and 0.11 (95% CI: -0.40-0.62), respectively. Conclusion: The effect of RIPC on cognitive performance in CABG patients remained insignificant. Results from previous studies were unable to justify the use of RIPC as a neuroprotective agent in CABG patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the knowledge, attitudes, and practice (KAP) toward postoperative cognitive dysfunction (POCD) among anesthesiologists in China. Methods: This cross-sectional study was conducted nationwide among Chinese anesthesiologists between December 2022 and January 2023. The demographic information and KAP scores of the respondents were collected using a web-based questionnaire. The mean KAP dimension scores ≥ 60% were considered good. Results: This study enrolled 1032 anesthesiologists (51.2% male). The mean total scores of knowledge, positive attitude, and positive practice were 9.3 ± 1.2 (max 12), 34.8 ± 3.3 (max 40), and 30.6 ± 6.7 (max 40), respectively. The knowledge items with correctness scores < 60% were "the anesthetic drugs that tend to cause POCD" (23.3%) and "Treatment of POCD" (40.3%). Multivariable analysis showed that ≥ 40 years old, master's degree or above, intermediate professional title (i.e., attending physician), senior professional title (i.e., chief physician), and working in tertiary hospitals were independently associated with adequate knowledge. Multivariable analysis showed that the attitude scores, middle professional title, and ≥ 16 years of experience were independently associated with good practice. Conclusions: These results suggest that Chinese anesthesiologists have good knowledge, favorable attitudes, and good practice toward POCD. Still, some points remain to be improved (e.g., the drugs causing POCD and managing POCD) and should be emphasized in training and continuing education. Trial registration: ChiCTR2200066749. [ABSTRACT FROM AUTHOR]

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype. [ABSTRACT FROM AUTHOR]

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Study objective: This meta-analysis aimed to assess whether continuous intravenous administration of DEX during surgery can be part of the measures to prevent the onset of postoperative delirium and postoperative cognitive dysfunction in elderly individuals following regional anesthesia. Methods: We searched the databases of PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (by June 1, 2023) for all available randomized controlled trials assessing whether intravenous application of dexmedetomidine can help with postoperative delirium and postoperative cognitive dysfunction in the elderly with regional anesthesia. Subsequently, we carried out statistical analysis and graphing using Review Manager software (RevMan version 5.4.1) and STATA software (Version 12.0). Main results: Within the scope of this meta-analysis, a total of 18 randomized controlled trials were included. Among them, 10 trials aimed to assess the incidence of postoperative delirium as the primary outcome, while the primary focus of the other 8 trials was on the incidence of postoperative cognitive dysfunction. The collective evidence from these 10 studies consistently supports a positive relationship between the intravenous administration of dexmedetomidine and a decreased risk of postoperative delirium (RR: 0.48; 95%CI: 0.37 to 0.63, p < 0.00001, I2 = 0%). The 8 literature articles and experiments evaluating postoperative cognitive dysfunction showed that continuous intravenous infusion of dexmedetomidine during the entire surgical procedure exhibited a positive preventive effect on cognitive dysfunction among the elderly population with no obvious heterogeneity (RR: 0.35; 95%CI: 0.25 to 0.49,p < 0.00001, I2 = 0%). Conclusion: Administering dexmedetomidine intravenously during surgery can potentially play a significant role in preventing postoperative delirium and postoperative cognitive dysfunction in patients older than 60 years with regional anesthesia according to this meta-analysis. [ABSTRACT FROM AUTHOR]