This study investigates the therapeutic effects and mechanisms of electroacupuncture (EA) on cognitive impairment induced by chronic hypoxia (CH) in mice. Chronic hypoxia was simulated by exposing mice to a 10 % oxygen environment for 8 hours daily over 3 months. The cognitive functions of the mice were assessed through behavioral tests, including the open field test (OFT), Y-maze, and Morris water maze (MWM). Results showed that CH induced significant anxiety-like behaviors and memory impairments in mice. EA treatment, targeting the Baihui (GV20), Shenting (GV24), and Zusanli (ST36) acupoints, significantly ameliorated these behavioral deficits. Histological analyses using HE staining, Nissl staining, and TUNEL assays demonstrated that EA reduced neuronal damage, apoptosis, and myelin loss in the cerebral cortex and hippocampus. Additionally, EA treatment significantly lowered the expression of the pro-inflammatory cytokine TNF-α in brain tissues, suggesting its anti-inflammatory effects. Immunofluorescence and Western blot analyses revealed that EA inhibited the overactivation of microglia and astrocytes in the CH model. Specifically, EA suppressed the expression of Iba1 and GFAP, markers of microglial and astrocytic activation, respectively. Furthermore, EA promoted the polarization of microglia towards the M2 anti-inflammatory phenotype by downregulating iNOS and upregulating Arg1. Similarly, EA reduced the expression of C3, a marker of A1 astrocytes, thereby preventing astrocytic polarization towards the pro-inflammatory state. Organotypic brain slice cultures subjected to oxygen-glucose deprivation (OGD) confirmed that electrical stimulation, akin to EA, inhibited the activation of microglia and astrocytes under hypoxic conditions. In conclusion, EA improves cognitive function in CH-induced mice by reducing neuroinflammation, inhibiting glial cell overactivation, and promoting anti-inflammatory phenotypes. These findings highlight EA's potential as a therapeutic intervention for cognitive impairments related to chronic hypoxia.

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases. In-hospital mortality was 1.4% (n = 393,157), and 4.4% of cases (n = 1,245,898) experienced perioperative organ injury. Perioperative organ injury was associated with 9-fold higher odds of death and prolonged hospital stay by 11.2 days. Acute kidney injury had the highest incidence (2.0%) and was associated with 25.0% mortality. While delirium had the second highest incidence (1.5%), it was associated with the lowest mortality (10.8%). This was followed by acute myocardial infarction (incidence 0.6%, mortality 15.6%), stroke (incidence 0.6%, mortality 13.1%), pulmonary embolism (incidence 0.3%, mortality 20.0%), liver injury (incidence 0.1%, mortality 68.7%), and acute respiratory distress syndrome (incidence 0.1%, mortality 44.7%). These findings help prioritize interventions for preventing or treating individual types of perioperative organ injury.

Perioperative neurocognitive dysfunction (PND) is influenced by various perioperative factors. Recent studies suggest that neuromuscular blocking reversal agents (NMBRs) may impact on PND. However, the results have been inconsistent. Therefore, we aimed to compare the effects of perioperative NMBRs on PND through this systematic review and meta-analysis.

We searched PubMed, CENTRAL, Embase, Web of Science, Scopus, and China Biology Medicine from their inception until May 2024. Two reviewers independently identified randomized controlled trials (RCTs) that compared the perioperative use of NMBRs with either a placebo or other NMBRs in patients undergoing general anaesthesia. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The primary outcome was the incidence of PND within 7 days following surgery, while the secondary outcomes included the time required to achieve a Train-of-Four ratio (TOF) ≥ 0.9 after administration of NMBRs, length of stay (LOS) in both the post-anaesthesia care unit (PACU) and the hospital, as well as the risk of adverse events (i.e. postoperative nausea and vomiting (PONV) and mortality).

A total of 10 randomized controlled trials involving 1705 patients compared the effects of NMBRs on PND. Neostigmine and sugammadex are the most commonly used NMBRs in clinical anaesthesia practice. In the primary analyses of all regimens, sugammadex significantly reduced the incidence of PND compared to neostigmine (risk ratio [RR] 0.67; 95% confidence interval [CI]:0.48-0.94; I2 = 0%; P = 0.02; moderate quality). However, the results indicated that there is no significant association between neostigmine and PND when compared to placebo (RR 0.76; 95% CI: 0.55-1.05; I2 = 35%; P = 0.09; moderate quality). The secondary outcomes revealed that sugammadex could significantly shorten the time of TOF ≥ 0.9 compared to neostigmine (mean difference [MD] -4.52; 95%CI: -5.04 to -3.99; I2 = 80%; P < 0.01; Moderate quality). Furthermore, no significant differences were observed in the incidence of adverse events or hospital LOS.

This meta-analysis demonstrated that the use of sugammadex was associated with improved early perioperative neurocognitive function compared to neostigmine when used to reverse neuromuscular blockade, without an increase in the incidence of adverse events.

PROSPERO CRD42024520287.

General anesthetics (GAs) are conventionally thought to induce loss of consciousness (LOC) by acting on pre- and post-synaptic targets. However, the mechanism underlying the involvement of astrocytes in LOC remains unclear. Here we report that inhaled GAs cause reversible impairments in the fine processes of astrocytes within the somatosensory cortex, mediated by regulating the phosphorylation level of Ezrin, a protein critical for the fine morphology of astrocytes. Genetically deleting Ezrin or disrupting its phosphorylation was sufficient to decrease astrocyte-synapse interaction and enhance sensitivity to sevoflurane (Sevo) in vivo. Moreover, we show that disrupting astrocytic Ezrin phosphorylation boosted the inhibitory effect of Sevo on pyramidal neurons by enhancing tonic GABA and lowering excitability under anesthesia. Our work reveals previously unappreciated phosphorylation-dependent morphological dynamics, which enable astrocytes to regulate neuronal activity during the transition between two brain consciousness states.

This study aimed to investigate the predictive effect of hemoglobin to red cell distribution width ratio (HRR) on postoperative delirium (POD) in older patients undergoing hip fracture surgery.

POD was diagnosed by capturing descriptive words from the medical records. The correlation between POD and HRR was determined using logistic regression analysis, and the receiver operating characteristic curve was used to further evaluate the value of HRR in predicting POD.

In total, 202 older patients accepting hip fracture surgery were included in our study. The result of multiple logistic regression analysis presented HRR (odds ratio, 0.504 [95% confidence interval, 0.340-0.747]; P < 0.001), American Society of Anesthesiologists physical status >2, and neutrophils were independently correlated with POD. The area under the curve of HRR was 0.746 (95% confidence interval, 0.676-0.815), and the optimal cutoff value was 8.322.

HRR, American Society of Anesthesiologists physical status >2 and neutrophils could independently predict POD in older patients undergoing hip fracture surgery, and HRR had satisfactory predictive value. However, further research is needed to confirm our findings. Geriatr Gerontol Int 2025; 25: 565-571.

This study aimed to assess the severity of postoperative delirium (PD) in elderly patients who underwent reverse total shoulder arthroplasty (rTSA) for irreparable massive rotator cuff tears (mRCTs) under general anesthesia (GA) compared to those under interscalene block (IB).

Forty elderly patients aged 65 years or older diagnosed with an irreparable mRCT who underwent rTSA were included in the prospective case-controlled study. Of these, 20 patients were operated under GA and the other 20 under IB. The average age was 77.1 years (range, 65-95 years). The severity of delirious symptoms was evaluated by the Delirium Rating Scale-revised-98 (DRS) score from the patients or guardians before the surgery and at 0, 3, and 7 days and 1, 3, and 6 months after the surgery and compared between the 2 groups.

Immediately after surgery, the visual analog scale score difference between the groups was statistically significant, with the GA group at 6.25 (standard deviation, ± 0.85) and the IB group at 3.80 (± 0.62) (p < 0.001). On the day of operation, the mean DRS score in the GA and IB groups were 9.10 (± 5.63) and 6.60 (± 5.33), respectively (p = 0.157). On day 3 of surgery, the mean DRS score in the GA group peaked to 9.95 (± 8.73), while in the IB group, it declined to 6.40 (±5.81) (p = 0.138). After 3 days, DRS scores showed a decreasing trend in both groups. When comparing the mean change (Δ) from the preoperative baseline scores to the postoperative values, the ΔDRS score was significantly higher with 4.15 (± 4.53) points in the GA group as compared to 1.30 (± 1.92) in the IB group (p = 0.014).

IB can be an attractive and efficient anesthetic choice in preventing PD for elderly patients undergoing rTSA for irreparable mRCTs. The IB group showed lower DRS scores and a peak on day 0 compared to the higher DRS scores and peak on day 3 in the GA group. Additionally, IB showed less pain than GA.

This article explored the application of dexmedetomidine (Dex), a highly selective alpha-2 agonist, in managing postoperative cognitive dysfunction (POCD) in elderly patients undergoing radical colon cancer surgery. Aging is associated with a progressive decline in physiological functions and an increased risk of adverse surgical outcomes, including POCD, which encompasses many neurocognitive disorders that manifest during the perioperative period. The aging population is at a higher risk for POCD, which can lead to prolonged hospital stays, delayed recovery, and increased healthcare costs. Dex has neuroprotective, opioid-sparing, and sympatholytic properties, which reduces the incidence and severity of POCD. Dex was introduced for sedation in patients receiving mechanical ventilation but has since been adopted in anesthesia due to its multifaceted benefits. Its application extends to sedation, analgesia, maintenance of anesthesia, and controlling delirium. Its neuroprotective and anti-inflammatory effects have been explored in managing POCD. This article discussed the broad range of patient and procedure-related risk factors for POCD. Early identification and intervention are crucial to prevent the progression of POCD, which can have severe physical, psychological, and economic consequences. The article underscored the importance of a multidisciplinary approach in managing POCD, involving the optimization of comorbidities, depth of anesthesia monitoring, hemodynamic stability, and cerebral oxygenation monitoring.

Postoperative delirium (POD) is a serious neuropsychiatric complication in elderly surgical patients, yet its pathogenesis remains incompletely understood. Transfer RNA-derived small RNAs (tsRNAs) have emerged as crucial regulators in neurological disorders. We investigated whether specific tsRNAs could serve as predictive biomarkers for POD.

This study conducted a prospective case-control study of 158 elderly patients (≥60 years) undergoing orthopedic surgery. Plasma samples were collected preoperatively and on postoperative day 3.tsRNA expression profiles were analyzed using RNA sequencing and validated by RT-qPCR. Propensity score matching was performed to balance demographic and clinical variables. The predictive value of candidate tsRNAs was assessed using ROC analysis, and their potential functions were explored through bioinformatic analyses.

Among 128 non-POD and 30 POD patients, two tsRNAs (Other-14: 31-tRNA-Gly-CCC-3 and Other-39: 73-tRNA-Arg-TCG-5) showed significantly elevated preoperative levels in POD patients (p<0.001).ROC analysis revealed strong predictive performance (AUC=0.868 and 0.956, respectively).These differences persisted in the propensity-matched cohort (29 pairs).Bioinformatic analyses indicated enrichment in pathways related to neurotransmission, inflammation, and metabolism.

This study identified novel tsRNA biomarkers that robustly predict POD risk and provide insights into its molecular pathogenesis. These findings may facilitate early risk stratification and preventive interventions.

Sepsis-associated encephalopathy (SAE) critically contributes to poor prognosis in septic patients. Identifying and screening key genes responsible for SAE, as well as exploring potential targeted therapies, are vital for improving the management of sepsis and advancing precision medicine.

Single-cell RNA sequencing (scRNA-seq) was administrated to identify cell subpopulations related to poor prognosis in septic patients. Next, hierarchical dynamic weighted gene co-expression network analysis (hdWGCNA) was employed to identify genes associated with specific neutrophil subpopulations. Enrichment analysis revealed the biological functions of these genes. Subsequently, neuroinflammation-related genes were obtained to construct a neuroinflammation-related signature. The AddModuleScore algorithm was used to calculate neuroinflammation scores for each cell subpopulation, whereas the CellCall algorithm was used to assess the crosstalk between neutrophils and other cell subpopulations. To identify key genes accurately, four binary classification machine learning algorithms were utilized. Finally, Western blotting and behavioral tests were used to confirm the role of LCN2-related neuroinflammation in septic mice.

This study utilized scRNA-seq to reveal the critical role of peripheral neutrophils during sepsis, identifying these neutrophils as contributors to poor prognosis and associated with neuroinflammation. On the basis of various machine learning algorithms, we discovered that Lipocalin-2 (LCN2) may be the key gene involved in neutrophil-induced SAE. To prove these findings, we conducted in vivo experiments and an animal model. Increased LCN2 expression and cognitive dysfunction occurred in septic mice. Additionally, the levels of markers of astrocytes and microglia and inflammatory factors such as TNF-α and IL-6 were significantly increased. All these phenomena were reversed by the downregulation of LCN2.

The upregulation of LCN2 expression on peripheral neutrophils is a critical step that triggers neuroinflammation in the central nervous system during SAE.

Postoperative neurocognitive disorders (PND) represent a significant challenge affecting patients undergoing surgical procedures, particularly in the elderly population. These disorders can lead to profound impairments in cognitive function, impacting memory, attention, and overall quality of life. Despite ongoing research efforts to identify risk factors and improve management strategies, PND remains underdiagnosed and poorly understood, complicating postoperative recovery and rehabilitation. This review aims to explore the recent advancement in the literature about PND, focusing on the underlying mechanisms, risk factors, and potential therapeutic approaches. We highlight recent advancements in the understanding of neuroinflammation, and it is implications for novel therapies to prevent PND. By synthesizing the latest research, we hope to provide insights that could lead to improved outcomes for patients at risk for PND and foster a shift towards more effective preventive measures in such population.

Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.

Postoperative cognitive dysfunction (POCD) is a significant surgery-related complication marked by cognitive decline. Studies indicated that neuroinflammation, ferroptosis, and mitochondrial fatty acid metabolism might play parts in POCD, and might be mediated by Carnitine palmitoyl transferase 1a (CPT1A), but requires further investigations. Therefore, this study aims to investigate the mechanism of mitochondrial fatty acid oxidase CPT1A on mitochondrial function, ferroptosis, and inflammation in POCD pathogenesis.

SVG P12 astrocytes were used to investigate CPT1A's control over mitochondrial function, ferroptosis, and inflammation affecting neurons. CPT1A was overexpressed using shRNA, with or without oligomycin to modulate mitochondrial function. Co-culture of these astrocytes with neurons, under similar conditions, assessed CPT1A's impact on neuron damage via ferroptosis and inflammation. Gene and protein expressions of CPT1A, SYN, PSD95 were measured via RT-PCR and WB. Detection of JC-1, mitochondrial oxygen consumption rate (OCR), ROS, Fe2+ concentration, MOD, SOD and GSH/GSSG using kits was conducted to explore mitochondrial function and ferroptosis. Inflammation was quantified by ELISA for IL-6, IL-1β, and TGF-β.

We successfully established CPT1A overexpression and knockdown models in astrocytes, confirming CPT1A's ability to enhance mitochondrial membrane potential. Elevated CPT1A levels led to improved mitochondrial function, synaptic integrity, reduced oxidative stress, maintained iron homeostasis, and attenuated neuroinflammation, as reflected by increased SYN, PSD95, OCR, GSH and SOD, decreased ROS,GSSG, MDA, iron levels, and lowered inflammatory factors expression. Treatment with oligomycin reversed these protective effects, demonstrating the dependency of CPT1A's benefits on intact mitochondrial respiration. In co-culture experiments with hippocampal neurons, astrocytes with manipulated CPT1A levels, particularly those co-treated with oligomycin, exacerbated neuronal mitochondrial dysfunction, oxidative stress, iron accumulation, and inflammation.

Overexpression of mitochondrial fatty acid oxidase CPT1A might improve synaptic integrity and rescue POCD by ameliorating astrocyte ferroptosis and neuroinflammation.

Perioperative cognitive dysfunction is a common complication in stroke patients undergoing secondary surgeries. This study investigated the effects of tibial fracture internal fixation (TFIF) surgery on cognitive function and the gut microbiota in mice with a history of stroke. Using the middle cerebral artery occlusion method to induce stroke, we assessed cognitive function via the fear conditioning test and analyzed the gut microbiota through 16S rRNA sequencing. Compared with those in the normal and stroke groups, the cognitive function of the mice in the stroke group that underwent TFIF surgery was significantly impaired. Gut microbiota analysis revealed significant changes in beta diversity, but not in alpha diversity, in these mice. Additionally, TFIF surgery increased microglial activation and IL-1β and lipopolysaccharide (LPS) levels in the brain while reducing α-defensin levels and increasing IL-1β and LPS levels in the colon. These results suggest that TFIF surgery exacerbates cognitive impairment in stroke mice, possibly through alterations in the gut microbiota that impair intestinal defense and promote inflammation. This study highlights the critical role of the gut microbiome in cognitive function and perioperative outcomes, offering insights into potential therapeutic strategies for perioperative cognitive dysfunction in stroke patients.

Postoperative neurocognitive disorders (PNDs) are frequent and serious perioperative complications in the elderly, and are associated with increased morbidity and mortality, length of hospital stay, and need for long-term care. At present, the pathogenesis of PND is not completely clear, and there are various risk factors including surgical trauma and stress mediating systemic inflammation towards neuroinflammation development which causes brain structural and functional changes namely PND. For elderly patients, perioperative neurological monitoring may provide insights into brain function status. Monitoring may also help clinicians identify potential risks which would ultimately allow timely and effective intervention for better perioperative safety and prognosis for elderly patients. In this review, we summarize the risk factors and potential mechanisms of PND, and discuss preliminary evidence regarding application of electroencephalography, functional near-infrared spectroscopy, functional magnetic resonance, and positron emission tomography imaging in monitoring the central nervous system during the postoperative period.

Perioperative neurocognitive disorders (PNDs), including postoperative delirium, delayed neurocognitive recovery, and long-term postoperative neurocognitive disorders, present significant challenges for older patients undergoing surgery. Inflammation is a protective mechanism triggered in response to external pathogens or cellular damage. Historically, the central nervous system (CNS) was considered immunoprivileged due to the presence of the blood-brain barrier (BBB), which serves as a physical barrier preventing systemic inflammatory changes from influencing the CNS. However, aseptic surgical trauma is now recognized to induce localized inflammation at the surgical site, further exacerbated by the release of peripheral pro-inflammatory cytokines, which can compromise BBB integrity. This breakdown of the BBB facilitates the activation of microglia, initiating a cascade of neuroinflammatory responses that may contribute to the onset of PNDs. This review explores the mechanisms underlying neuroinflammation, with a particular focus on the pivotal role of cytokines in the pathogenesis of PNDs.

Esketamine ameliorates propofol-induced brain damage and cognitive impairment in mice. However, the precise role and underlying mechanism of esketamine in perioperative neurocognitive disorders (PND) remain unclear. Therefore, this study aimed to investigate the key genes associated with the role of esketamine in PND through animal modeling and transcriptome sequencing.

The present study established a mice model of PND and administered esketamine intervention to the model, and mice were divided into control, surgical group, and surgical group with esketamine. Behavioral assessments were conducted using the Morris water maze and Y maze paradigms, while transcriptome sequencing was performed on hippocampal samples obtained from 3 groups. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on sequencing data to identify candidate genes related to esketamine treating PND. Thereafter, protein-protein interaction (PPI) network analysis was implemented to select key genes. The genes obtained from each step were subjected to enrichment analysis, and a regulatory network for key genes was constructed.

The Morris water maze and Y maze findings demonstrated the successful construction of our PND model, and indicated that esketamine exhibits a certain therapeutic efficacy for PND. Ank1, Cbln4, L1cam, Gap43, and Shh were designated as key genes for subsequent analysis. The 5 key genes were significantly enriched in cholesterol biosynthesis, nonsense mediated decay (NMD), formation of a pool of free 40s subunits, major pathway of rRNA processing in the nucleolus and cytosol, among others. Notably, the miRNAs, mmu-mir-155-5p and mmu-mir-1a-3p, functionally co-regulated the expression of Ank1, Gap43, and L1cam.

We uncovered the therapeutic efficacy of esketamine in treating PND and identified 5 key genes (Ank1, Cbln4, L1cam, Gap43, and Shh) that contribute to its therapeutic effects, providing a valuable reference for further mechanistic studies on esketamine's treatment of PND.

Postoperative neurocognitive disorder (PND) is a cognitive decline after general anesthesia and surgery, influenced by preexisting neurodegenerative conditions, stress, and inflammation. Traumatic brain injury (TBI) is linked to a dysregulated stress response, neuroinflammation, and cognitive issues. Patients with TBI often need extracranial surgeries under general anesthesia (GA), which can increase stress, neuroinflammation, and neurodegenerative changes, raising PND risk. We will search databases like Ovid Medline and Embase for studies on cognitive function in patients with mild to moderate TBI who had extracranial surgeries under general anesthesia (GA). Screening and data extraction will be done manually and with AI-assisted tools (ASReview). Study quality will be assessed using the Newcastle-Ottawa Scale. Statistical analyses will include mean differences, odds ratios, and meta-regression, addressing heterogeneity, sensitivity, and publication bias using Stata/SE. By meta-analyzing clinical studies, we aim to determine if TBI and GA/surgery interact to induce PND. We will use various data sources, subgroup analyses, sensitivity analyses, and meta-regression to assess factors like age, gender, and type of GA/surgery. This meta-analysis will enhance our understanding of PND risks, inform clinical practices, and highlight new research directions. The systematic review is registered in PROSPERO (CRD42024510980).

Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador.

We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least squares regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes.

Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.465 units (95% CI: -0.80, -0.13) and -0.418 units (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.112 units (-0.19, -0.03). A greater inflammatory composite variable from seven markers was associated with lower scores in language (β = -0.11, p = 0.043), visuospatial processing (β = -0.15, p = 0.086), and social perception (β = -0.22, p = 0.005) domains.

Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

Systemic inflammation after heart valve replacement surgery commonly results in complications including cognitive impairment. This study was designed to investigate whether valvular heart disease itself and inflammation after valve replacement surgery affects cognition and the related functional connectivity (FC) of the hippocampal memory network.

Forty-three patients with valvular heart disease were screened for recruitment and assessed with cognition function tests, blood inflammatory cytokine measurements, and functional magnetic resonance imaging scans before surgery and on postoperative day 7 and 30. Age- and sex-matched healthy controls (n=30) were recruited for comparison. The brain FC networks using the hippocampus as a seed were analysed. Bivariate correlation and structural equation model analyses were carried out to investigate the association between altered FC, memory, and inflammation.

Thirty-five patients and 29 healthy controls completed the study, and their data were finally analysed and reported. Compared with healthy controls, the surgery group had increased FC in the bilateral precuneus and middle cingulate and paracingulate gyri before surgery. They exhibited impaired memory, increased plasma concentrations of proinflammatory cytokines, and decreased hippocampal FC at postoperative day 7. At 30 days after surgery, the FC abnormalities seen before surgery and at postoperative day 7 were restored to the level comparable with the healthy controls. High systemic inflammation was significantly associated with worse memory and lower FC in the hippocampal memory network.

Valve replacement surgery temporarily disrupts the hippocampal memory network with transient associated memory decline.

ChiCTR2300069614.

Postoperative cognitive dysfunction (POCD) is a common complication after total knee arthroplasty (TKA), impacting recovery and quality of life. This study aims to investigate central sensitization (CS) as an independent risk factor for POCD to improve preoperative screening and postoperative interventions.

A retrospective analysis was conducted on 142 TKA patients from January 2020 to May 2024 across three hospitals. Data were collected at six time points: preoperatively (T0), intraoperatively (T1), and postoperatively on days 1 (T2), 3 (T3), 7 (T4), and 30 (T5). Patients were classified into CS (CSI ≥ 40) and non-CS (CSI < 40) groups according to Central Sensitization Inventory (CSI) score. Cognitive function and POCD incidence were assessed with the Mini-Mental State Examination (MMSE), and knee recovery with the Knee Injury and Osteoarthritis Outcome Score (KOOS). Logistic regression was used to identified risk factors for POCD.

The overall incidence of POCD at T5 was 19.72%, with a significantly higher rate in CS group (30.91%) compared to non-CS group (12.64%) (p = 0.008). MMSE scores declined significantly in both groups at T2 and T3 compared to T0 (p < 0.05), with CS group showing consistently lower scores than non-CS group at T2-T5 (p < 0.05). KOOS scores revealed that CS group had worse pain and quality of life scores at T0, T4, and T5 compared with non-CS group (p < 0.05). Logistic regression revealed that CS, cerebrovascular disease, intraoperative hemorrhage, and preoperative MMSE were associated with the risk of POCD (p < 0.05).

CS is a significant risk factor for POCD following TKA, adversely affecting recovery in terms of pain and quality of life. Prospective studies are warranted to validate findings and develop targeted interventions.

Sepsis-associated encephalopathy (SAE) is a serious condition in which the immune system uncontrollably responds to infection, causing organ dysfunction. Neuroinflammation is one of the primary mechanisms underlying SAE. N6-methyladenosine (m6A) methylation is a common and reversible chemical modification of RNA molecules. Increasing evidence suggests that this modification plays a vital role in the inflammatory immune response. AlkB homolog 5 (ALKBH5) is an enzyme responsible for removing m6A modifications from RNA molecules and is known as a demethylase. However, the specific role of ALKBH5 in neuroinflammation remains unclear. To explore the role of ALKBH5 in neuroinflammation, researchers have used lipopolysaccharide (LPS) to induce inflammation in BV2 cells and mice. This study found that treatment of BV2 cells with LPS (1 μg/mL) significantly increased the total RNA m6A level and the ALKBH5 protein decreased significantly. Meanwhile, the NF-κB inflammatory signaling pathway was activated, leading to an obvious increase in IL-1β, IL-6, and TNF-α mRNA. The LPS-induced inflammatory response was alleviated when ALKBH5 was overexpressed in BV2 cells. This is due to a slower degradation rate of NFKBIA mRNA, an increase in NFKBIA protein levels, and inhibition of the NF-κB inflammatory signal pathway. When ALKBH5 was overexpressed in mice, as expected, there was an improvement in behavioral abnormalities induced by LPS. Compared to healthy volunteers, ALKBH5 mRNA levels were significantly decreased in peripheral blood mononuclear cells (PBMCs) from patients with sepsis and correlated with GCS and IL-6 levels. In summary, this study suggested that ALKBH5 is a potential therapeutic target for enhancing NFKBIA mRNA stability and alleviating neuroinflammation. Thus, ALKBH5 may provide new insights into the diagnosis and treatment of SAE.

Remimazolam, a novel benzodiazepine, is widely used as an anesthetic in endoscopic procedures; however, its effects on cognitive function remain unclear, limiting its broader application in general anaesthesia. Neuroinflammation is a well-established key factor in the etiology and progression of cognitive dysfunction, including conditions such as Alzheimer's disease, Parkinson's disease, postoperative delirium, and postoperative cognitive dysfunction. Preclinical studies have demonstrated that remimazolam exerts anti-inflammatory and neuroprotective effects, and clinical reports indicate a reduced incidence of postoperative delirium in patients treated with remimazolam. Nevertheless, whether remimazolam improves cognitive function through its anti-inflammatory properties remains uncertain. This study aimed to investigate the neuroprotective effects of remimazolam and its underlying mechanism in a lipopolysaccharide (LPS)-induced model of neuroinflammation, neuronal injury, and cognitive dysfunction METHODS: C57BL/6 J male mice were administered LPS intraperitoneally to establish a model of neuroinflammation-induced cognitive impairment. A subset of mice received remimazolam via intraperitoneal injection 30 minutes prior to LPS administration. Cognitive performance was evaluated using behavioural tests, including the Morris Water Maze (MWM), Novel Object Recognition (NOR) test, and Open Field Test (OFT). Hippocampal tissues were analyzed by haematoxylin-eosin (HE) staining to assess structural changes. Inflammatory markers, including Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, were quantified using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR. Immunofluorescence was used to detect translocator protein (TSPO) and markers of microglia activation (IBA-1, CD16/32, and CD206).

(1) Remimazolam reversed LPS-induced cognitive deficits, as evidenced by shorter spatial exploration latency and increased platform crossings in the MWM, and an elevated recognition index in the NOR test. (2) Remimazolam improved hippocampal morphology, reducing LPS-induced neuronal damage. (3) Remimazolam significantly decreased levels of hippocampal inflammatory cytokines, inhibited microglial activation, promoted M2-type microglia polarization, and increased TSPO expression.

Remimazolam demonstrated neuroprotective and anti-neuroinflammatory effects in a mouse model of LPS-induced cognitive impairment. These effects are likely mediated through the regulation of TSPO, which inhibits microglial activation and promotes the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.

CD3(+) CD4(-) CD8(-) double negative T cells (DNTs) manifest themselves in autoimmune diseases and associated inflammation. In the central nervous system, the increased presence of DNTs is associated with the progression of neurological conditions and brain injury. Active DNTs that produce IL-17 have been regarded as a pro-inflammatory phenotype. The IL-17 signaling pathway mediates neuroinflammatory responses by inducing glial activation and producing inflammatory factors. Neuroinflammation is considered integral to the pathogenesis of perioperative neurocognitive disorders (PNDs), commonly developed after surgery in susceptible patients. We and others have demonstrated a significant role for complement C3 in surgery-induced neuroinflammation and cognitive impairment but the regulatory mechanisms for this remain unexplored. We hypothesized that surgery induces DNT infiltration into the CNS that in turn upregulates complement C3 expression and this causes changes that contribute to cognitive impairment. Using an adult murine abdominal surgery model, we investigated perioperative changes in cognitive performance, quantifying the presence of T cell subsets and phenotype, IL-17 signaling pathway activation, glial cell activation and C3 expression in the brain. Postoperative IL-17 specific inhibitor GSK2981278 administration or preoperatively conditional CEBPβ knock-down by AAV9 viral vector were then applied to evaluate the effect of inhibiting IL-17 signaling pathway on postoperative C3 expression and cognitive performance. The results showed an increased hippocampus infiltration of DNTs with augmented IL-17 production, along with C3 upregulation and cognitive impairment. Both inhibition of IL-17 or knock-down of CEBPβ significantly suppressed C3 expression, synaptic engulfment by microglia and attenuated cognitive impairment. These findings indicate that DNTs promote postoperative neuroinflammation and cognitive impairment via the IL-17/CEBPβ/C3 pathway and targeting this IL-17 axis could be a potential therapeutic strategy to ameliorate postoperative neuroinflammation and cognitive impairment.

Epidemiological evidence associates Toxoplasma gondii latent infection with the development of neuropsychiatric disorders, and various immunological and environmental factors play key pathophysiological roles through host immune response alterations. We investigated the cognitive and motor alterations occurring in the terminal stage of T. gondii infection in rats, and whether a low-protein diet, a high-fat diet or ovariectomy may accelerate their development, given the role of malnutrition and menopause on immunity and resistance to infection. In two sets of experiments, 2-month-old (157.5 ± 4.3 g, n = 42) male (n = 18) and female (n = 24) Wistar rats were infected with T. gondii (ATCC 40050). Open-field and elevated plus maze tests were performed in the terminal stage of infection first and then in the early stage in low-protein diet-fed, high-fat diet-fed and ovariectomized infected rats. Late-stage (90 days) infected and early-stage (17 days) low-protein diet-fed groups showed significant decreases in body weight (42.42%↓, P = 0.016 and 57.14%↓, P < 0.001 versus non-infected, respectively), increases in body temperature (P = 0.001 and P < 0.001, respectively), decreases in blood glucose levels (P = 0.006 and P = 0.020, respectively), signs of cognitive and motor impairment and lower neuron counts. The alterations observed in high-fat diet-fed and ovariectomized infected animals were milder. Low-protein diet feeding to T. gondii-infected rats accelerated the occurrence of the infection terminal stage. Thus, a diet low in proteins could transform a slow early-stage T. gondii infection into an active neurotoxoplasmosis with neuropsychiatric manifestations and possible neurodegeneration in rats.

Post-operative delirium is a dreaded complication after surgery in older patients. The identification of risk factors for delirium and comprehensive geriatric assessment is an extensive part of recent research. However, the preoperative assessment of risk factors, such as impaired cognition, is frequently not standardized.

A comprehensive preoperative assessment was performed in 421 surgical patients to investigate the impact of preoperative cognitive impairment (PCI) on the risk of delirium and to evaluate appropriate screening tools (Six-item screener (SIS) and clock-drawing test (CDT)).

Both screening tools showed a significantly increased risk of delirium with p < 0.001 (OR 12.5, 95% [6.42; 24.4]) in SIS and p = 0.042 (OR 2.02, 95%CI [1.02; 4.03]) in CDT for existing cognitive impairment. A higher level of care (p < 0.001) and statutory care (p < 0.001, OR 5.42, 95%CI [2.34; 12.6]) also proved to be significant risk factors. The ROC curves of the two tests show AUC values of 0.741 (SIS) and 0.630 (CDT). The COP values for the SIS are 4 points with a Youden index of 0.447; for the CDT, the COP is 2 (Youden index = 0.177).

The recording of PCI should be a central component of the preoperative geriatric assessment. The tools used are simple yet effective and can be easily implemented in routine clinical practice. By reliably identifying patients at risk, the available resources can be personalized and used in a targeted approach.

Postoperative cognitive recovery is deeply important to patients and perioperative clinicians. Despite decades of data on "postoperative cognitive decline" (POCD), a research diagnosis based on objective cognitive test performance, perspectives on subjective cognitive complaints (SCC) after modern surgery/anesthesia have not been systematically collected or studied despite their recent inclusion in the 2018 redefinition of "postoperative neurocognitive disorder." The authors describe the alignment between SCC anecdotes and the research diagnosis of POCD, contextualizing these findings using recent literature within and outside anesthesiology. This article prepares anesthesiologists to discuss what is, and is not, known about subjective cognitive recovery after surgery/anesthesia.

To test the hypothesis that emergence delirium might be associated with worse long-term survival.

A longitudinal prospective observational study.

A tertiary hospital in Beijing, China.

A total of 942 patients aged 65-90 years who were admitted to post-anesthesia care unit (PACU) after major noncardiac surgery under general anesthesia.

Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay.

Patients were followed up once a year for at least 3 years. Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. Associations between emergence delirium and long-term survivals were analyzed with the Cox proportional hazard models.

Among enrolled patients, 915 completed perioperative assessments; 906 completed long-term follow-up (mean age 72 years; 60 % [545/906] male; 73 % [660/906] cancer surgery). At the end of follow-up (median 43 months), there were 69 deaths in 331 patients (21 %) with emergence delirium versus 114 deaths in 575 patients (20 %) without: unadjusted hazard ratio 1.10 (95 % CI: 0.81 to 1.48); P = 0.547; adjusted hazard ratio 0.96 (95 % CI: 0.70 to 1.32); P = 0.797. Recurrence-free survival was 73/331 (22 %) in patients with emergence delirium versus 121/575 (21 %) without: unadjusted hazard ratio 1.08 (95 % CI: 0.81 to 1.45); P = 0.598; adjusted hazard ratio 0.94 (95 % CI: 0.69 to 1.28); P = 0.695. Event-free survival was 159/331 (48 %) in patients with emergence delirium versus 268/575 (47 %) without: unadjusted hazard ratio 1.06 (95 % CI: 0.87 to 1.29); P = 0.563; adjusted hazard ratio 0.98 (95 % CI: 0.80 to 1.21); P = 0.875.

We did not find significant association between emergence delirium and worse long-term survival in older patients after general anesthesia and major surgery mainly for cancer. The effects of emergence delirium on long-term outcomes deserve further investigation.

www.chictr.org.cn; ChiCTR-OOC-17012734.

Currently, the diagnosis of delirium is solely based on clinical observation, lacking objective diagnostic tools, and the regulatory networks and pathological mechanisms behind it are not yet fully understood. Exosomes have garnered considerable interest as potential biomarkers for a variety of illnesses. This research aimed to delineate both the proteomic and metabolomic landscapes inherent to exosomes, assessing their diagnostic utility in postoperative delirium (POD) and understanding the underlying pathophysiological frameworks. Integrated analyses of proteomics and metabolomics were conducted on exosomes derived from plasma of individuals from both the non-postoperative delirium (NPOD) control group and the POD group. Subsequently, the study utilized the Connectivity Map (CMap) methodology for the identification of promising small-molecule drugs and carried out molecular docking assessments to explore the binding affinities with the enzyme MMP9 of these identified molecules. We identified significant differences in exosomal metabolites and proteins between the POD and control groups, highlighting pathways related to neuroinflammation and blood-brain barrier (BBB) integrity. Our CMap analysis identified potential small-molecule therapeutics, and molecular docking studies revealed two compounds with high affinity to MMP9, suggesting a new therapeutic avenue for POD. This study highlights MMP9, TLR2, ICAM1, S100B, and glutamate as key biomarkers in the pathophysiology of POD, emphasizing the roles of neuroinflammation and BBB integrity. Notably, molecular docking suggests mirin and orantinib as potential inhibitors targeting MMP9, providing new therapeutic avenues. The findings broaden our understanding of POD mechanisms and suggest targeted strategies for its management, reinforcing the importance of multidimensional biomarker analysis and molecular targeting in POD intervention.

The decrease in sleep quality leads to an increased risk of cardiovascular disease and is closely related to the prognosis of various diseases. However, the relationship between preoperative sleep quality and postoperative clinical outcomes in patients with acute aortic dissection is still unclear. We aimed to assess the relationship between sleep quality and the clinical outcomes of acute aortic dissection. We assessed participants' sleep quality and the clinical outcomes of acute aortic dissection, which included prolonged mechanical ventilation, postoperative delirium, in-hospital death, continuous renal replacement therapy, intensive care unit stay time, and length of stay. Patients were divided into good sleep quality group (n = 103) and poor sleep quality group (n = 113). Postoperative delirium, in-hospital death, prolonged mechanical ventilation and intensive care unit stay time were significantly increased in the poor sleep quality group when compared with the good sleep quality group (p < 0.05). Multivariate regression analysis showed that the poorer sleep quality, the greater the risk of in-hospital death (odds ratio = 3.451, 95% confidence interval 1.19-10.004) and prolonged mechanical ventilation (odds ratio = 6.302, 95% confidence interval 3.105-12.791), and the longer intensive care unit stay time (β = 62.37, 95% confidence interval 22.411-102.329). In addition, the higher the incidence of smoking history (odds ratio = 7.417, 95% confidence interval 2.425-22.684), poor sleep quality (odds ratio = 11.59, 95% confidence interval 3.844-34.942) and postoperative delirium (odds ratio = 5.1, 95% confidence interval 1.793-14.504), the greater the risk of prolonged mechanical ventilation. Our findings revealed that poor sleep quality may be a risk factor for adverse clinical outcomes of acute aortic dissection. Rapid assessment of self-reported sleep quality may be a simple and effective way to identify patients with acute aortic dissection who are at high risk for prolonged mechanical ventilation.

Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.

The decrease expression of PGC-1α contributes to perioperative neurocognitive disorders (PND). This study aimed to investigate the effects of the PGC-1α agonist ZLN005 in preventing PND and to explore the potential mechanism.

C57BL/6 mice were randomly divided into four groups: the control group (Group C), the surgery group (Group S), the surgery and ZLN005 (5 mg/(kg⋅d)) group (Group L), and the surgery and ZLN005 (7.5 mg/(kg⋅d)) group (Group H). Except for Group C, the other three groups received intraperitoneal injections of vehicle or ZLN005 once a day from 3 days before surgery to 3 days after surgery. The open field test, novel object recognition test and fear conditioning test were performed to measure anxiety behaviors, locomotor activity and memory. The levels of IL-6 and IL-1β were measured at 24 hours after surgery. ATP and ROS levels were measured at 3 days post-surgery. PGC-1α, NRF-1, Atp5d, Atp5k and Cox5a were measured at one day or three days post-surgery.

ZLN005 treatment improved the cognitive function of mice in Group L and Group H compared with Group S. The expression of IL-6 and IL-1β in the hippocampus of the S group was increased after surgery, and ZLN005 reduced the expression of IL-6 and IL-1β in the hippocampus of mice one day after surgery. There were parallel decreases in the expression of PGC-1α/NRF-1 and mitochondrial function in the hippocampus of the Group S mice compared with the Group C mice. The expression of PGC-1α/NRF-1 and mitochondrial function were upregulated after ZLN005 treatment.

Neuroinflammation and mitochondrial damage are involved in the occurrence of PND. ZLN005 activates PGC-1α to increase the expression of mitochondrial proteins, improve mitochondrial function, and ultimately ameliorate the cognitive status of mice after surgery.

Recent research has revolutionized our understanding of memory consolidation by emphasizing the critical role of astrocytes, microglia, and immune cells in through cytokine signaling. Cytokines, compact proteins, play pivotal roles in neuronal development, synaptic transmission, and normal aging. This review explores the cellular mechanisms contributing to cognitive decline in inflammaging and Alzheimer's disease, highlighting the paradoxical effects of most studied cytokines (IL-1, IL-6, TNF-α) in brain function, which act as a double-edged sword in brain physiology, acting both as facilitators of healthy cognitive function and as a potential contributor to cognitive decline.

Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador.

We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes.

Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.47 units (95% CI: -0.80, -0.13) and -0.42 (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.11 units (-0.19, -0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (-0.11 units, p=0.04), visuospatial processing (-0.15, p= 0.09), and social perception (-0.22, p=0.005) domains.

Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

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.

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.

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.

The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.

Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model.

C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3β (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed.

SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors.

Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

Myocardial ischemia-reperfusion (MI/R) can lead to structural and functional abnormalities in the hippocampal neurons of the brain. High-mobility group box-l (HMGB1) is implicated in the activation of immune cells and the stimulation of inflammatory responses. However, the specific role of HMGB1 in cognitive impairment induced by MI/R in elderly rats has yet to be elucidated.

Elderly rats underwent surgical procedures to induce MI/R. To evaluate the learning and memory abilities of these rats, a water maze test and a new-object recognition test were administered. Nissl staining was utilised to examine hippocampal neuron damage. Enzyme-linked immunosorbent assay, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to measure the expression levels of HMGB1, inflammatory cytokines, and molecular pathways.

The study found that MI/R induced cognitive impairment in elderly rats. There was an observed increase in serum HMGB1 levels, along with elevated concentrations of pro-inflammatory cytokines in the plasma and hippocampus, accompanied by a decrease in anti-inflammatory cytokines. Moreover, substantial damage was evident in the hippocampal neurons of rats exposed to MI/R. In the brains of these rats, there was an increased expression of HMGB1, the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), phosphorylated p65, interleukin-1β (IL-1β), IL-6, IL-23, tumour necrosis factor-α (TNF-α), caspase-3, and Bax. In contrast, the expression of B-cell lymphoma 2 was decreased. The RT-qPCR analyses indicated elevated levels of HMGB1, RAGE, TLR4, IL-1β, IL-6, IL-23, TNF-α, caspase-3, and Bax mRNA.

The increased concentration of serum and hippocampal inflammatory factors in the brains of elderly rats subjected to MI/R suggests that cognitive impairment may be induced through the activation of the HMGB1/TLR4/NF-κB signalling pathway.

Delirium is linked to brain abnormalities, yet the role of the glymphatic system is not well understood. This study aims to examine alterations in brain physiology in delirium by using diffusion-tensor imaging (DTI) to assess water diffusion along the perivascular space (ALPS) and to explore its correlation with clinical symptoms.

We examined 15 patients with delirium and 15 healthy controls, measuring water diffusion metrics along the x-, y-, and z-axes in both projection and association fibers to determine the DTI-ALPS index. We used a general linear model, adjusted for age and sex, to compare the DTI-ALPS index between groups. We also investigated the relationship between the DTI-ALPS index and clinical symptoms using partial correlations.

Patients with delirium exhibited significantly lower DTI-ALPS indices compared to healthy controls (1.25 ± 0.15 vs. 1.38 ± 0.10, t = 2.903, p = 0.007; 1.27 ± 0.16 vs. 1.39 ± 0.08, 1.22 ± 0.16 vs. 1.37 ± 0.14, t = 2.617, p = 0.014; t = 2.719, p = 0.011; respectively). However, there was no significant correlation between the DTI-ALPS index and clinical symptoms.

Our findings indicate a decreased DTI-ALPS index in patients with delirium, suggesting potential alterations in brain physiology that may contribute to the pathophysiology of delirium. This study provides new insights into the mechanisms underlying delirium.

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16 hours of fasting and 8 hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia.

Cognitive impairment is a common issue among human patients undergoing surgery, yet the neural mechanism causing this impairment remains unidentified. Surgical procedures often lead to glial cell activation and neuronal hypoexcitability, both of which are known to contribute to postoperative cognitive dysfunction (POCD). However, the role of neuron-glia crosstalk in the pathology of POCD is still unclear. Through integrated transcriptomics and proteomics analyses, we found that the complement cascades and microglial phagocytotic signaling pathways are activated in a mouse model of POCD. Following surgery, there is a significant increase in the presence of complement C3, but not C1q, in conjunction with presynaptic elements. This triggers a reduction in excitatory synapses, a decline in excitatory synaptic transmission, and subsequent memory deficits in the mouse model. By genetically knockout out C3ar1 or inhibiting p-STAT3 signaling, we successfully prevented neuronal hypoexcitability and alleviated cognitive impairment in the mouse model. Therefore, targeting the C3aR and downstream p-STAT3 signaling pathways could serve as potential therapeutic approaches for mitigating POCD.