Postoperative Cognitive Dysfunction Research Articles

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats dependent on NLRP3 activation

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats dependent on NLRP3 activation

Unraveling the role and mechanism of mitochondria in postoperative cognitive dysfunction: a narrative review

AbstractPostoperative 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.

17β-estradiol Ameliorates Postoperative Cognitive Dysfunction in Aged Mice via miR-138-5p/SIRT1/HMGB1 Pathway

Abstract Background Postoperative cognitive dysfunction (POCD) is a common neurological complication in older patients and correlated with adverse outcomes.17β-estradiol treatment was reported to provide neuroprotective protection in various neurologic disorders, but whether it attenuated POCD was unknown. The purpose of this study was to explore the effects of 17β-estradiol treatment on POCD and the mechanisms. Methods We generated a POCD model in 15-month-old mice via laparotomy, followed by subcutaneous injection of 17β-estradiol, intraperitoneal injection of EX527 (a SIRT1 inhibitor) or bilateral hippocampal injection of miR-138-5p-agomir. Morris water maze test and open field test were applied to evaluate the cognitive function. The neuronal apoptosis in hippocampus was detected using TUNEL assay. Meanwhile, the levels of IL-1β and microglia activation were measured by ELISA and immunofluorescence, respectively. Western blot was utilized to assess the expression of SIRT1 and HMGB1 protein, and gene expression of miR-138-5p was determined through qRT-PCR. Results Behavioral tests showed that 17β-estradiol treatment improved cognitive function in aged POCD mice. In addition, 17β-estradiol attenuated neuronal apoptosis and microglia activation as well as IL-1β expression in hippocampus. Nonetheless, injection with EX527 abolished the beneficial impacts of 17β-estradiol against POCD. Furthermore, miR-138-5p was verified to bind with SIRT1, which regulated the expression of HMGB1. After treatment with 17β-estradiol, miR-138-5p expression was reduced in hippocampus, and the neuroprotective influence of 17β-estradiol on aged POCD mice was reversed after administration of miR-138-5p-agomir. Conclusions 17β-estradiol treatment exerted neuroprotection effects on POCD in aged mice, which might be relevant to alleviating neuroinflammation via miR-138-5p/SIRT1/HMGB1 pathway.

Impact of intravenous infusion of lidocaine on intrapulmonary shunt and postoperative cognitive function in patients undergoing one-lung ventilation.

Intravenous infusion of lidocaine as an anesthesia adjuvant can improve patient outcomes, but its impact on intrapulmonary shunt during one-lung ventilation (OLV) has not been clarified. To determine the effect of intravenous lidocaine infusion on intrapulmonary shunt during OLV and postoperative cognitive function in video-assisted thoracoscopic surgery (VATS). Sixty patients who underwent OLV for thoracic surgery were randomized to receive intravenous infusion of lidocaine (lidocaine group, n = 30) or normal saline (control group, n = 30) for anesthesia induction. Arterial and venous blood gases were measured during two-lung ventilation and at 15 and 30 min after OLV (OLV + 15 and OLV + 30). The Mini-Mental State Examination was administered before the surgery and at postoperative 12 months to assess patient cognitive function. No significant difference was found in intrapulmonary shunt fraction (Qs/Qt) between the lidocaine group and the control group at OLV + 15 (p = 0.493) and OLV + 30 (p = 0.754). The lidocaine group used significantly lower doses of propofol and remifentanil compared to the control group (both p < 0.001). Furthermore, no significant difference was observed in the incidence of postoperative cognitive dysfunction between the lidocaine group and the control group at 1 year post-operation (3.3% vs 6.7%, p = 0.554). Intravenous lidocaine administered in VATS had no significant impact on intrapulmonary shunt during OLV or postoperative cognitive function. However, it significantly reduced the doses of anesthetics used during the surgery.

Boston Naming Test as a Screening Tool for Early Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.

The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.

CD200-CD200R Pathway: A Regulator of Microglial Polarization in Postoperative Cognitive Dysfunction

CD200-CD200R Pathway: A Regulator of Microglial Polarization in Postoperative Cognitive Dysfunction

Progress on the Mechanisms and Neuroprotective Benefits of Dexmedetomidine in Brain Diseases.

Dexmedetomidine, a highly specific α2 agonist, has been extensively utilized in clinical sedation and surgical anesthesia since its introduction in 2000 due to its excellent sympatholytic, sedative, and analgesic effects. This review aimed to identify new approaches for the treatment of patients with brain disorders by thoroughly describing the mechanism of action of dexmedetomidine and examining its neuroprotective effects from the standpoints of basic and clinical research. The PubMed and Web of Science databases were searched using the keywords dexmedetomidine and related brain diseases, although relevant articles from the last decade were included for detailed summarization and analysis. Dexmedetomidine has shown strong neuroprotective effects, such as protection of the blood-brain barrier, decreased neuronal death, maintained hemodynamic stability, and reduced postoperative agitation and cognitive dysfunction. Furthermore, dexmedetomidine has been shown to exert various neuroprotective effects, including anti-inflammatory and antioxidative stress effects, modulation of autophagy, and reduction of apoptosis in cerebral diseases. Dexmedetomidine acts as a neuroprotective agent against brain diseases during all phases of treatment. However, clinical trials with larger sample sizes are required to optimize dosage and dosing strategies.

Effects of cognitive training on cognitive function in patients after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials.

Postoperative cognitive deficits frequently occur in patients undergoing cardiac surgery, leaving them with reduced cognitive function. Cognitive training has been shown to improve cognitive function, however, the role in patients after cardiac surgery is unclear. In this study, we aimed to evaluate the effectiveness and safety of cognitive training in patients undergoing cardiac surgery. A systematic search of PubMed, Embase, Cochrane Library, CINAHL, Ovid Medline, Web of Science, CNKI, and Wanfang was conducted until March 2024. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Data were meta-analyzed using RevMan 5.4 software. Potential bias and reliability of evidence were fairly assessed by using the Cochrane risk of bias method and the GRADE evidence grading method. A total of 16 studies involving 1335 cardiac surgery patients were included in this study. Compared with the control group, the cognitive training group had a significantly lower incidence of postoperative cognitive dysfunction (RR 0.35, 95% CI 0.18-0.65, P = .001), significantly improved cognitive function (MD 2.54, 95% CI 1.27-3.81, P < .001), and a significantly higher quality of life-mental component (MD 5.22, 95% CI 2.32-8.13, P < .001), anxiety (MD -6.05, 95% CI -10.96 to -1.15, P = .02) and depression (MD -3.97, 95% CI -7.15 to -0.80, P = .01) were significantly improved between groups. However, the differences were not statistically significant for postoperative delirium (RR 1, 95% CI 0.38-2.65, P = 1.00) and postoperative hospitalization (MD -0.95, 95% CI -2.90 to 1.00, P = .34). The present study, based on a low to moderate quality of evidence, suggests that cognitive training improves cognitive functioning, reduces the incidence of postoperative cognitive dysfunction, and has a positive impact on anxiety and depression in patients undergoing cardiac surgery. However, current evidence does not allow for the determination of effects on quality of life, postoperative delirium, and postoperative length of stay.

IL-12p70 Induces Neuroprotection via the PI3K-AKT-BCL2 Axis to Mediate the Therapeutic Effect of Electroacupuncture on Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD), a postsurgical decline in cognitive function, primarily affects older adults and worsens their prognosis. Although elevated interleukin-12p70 (IL-12p70) is closely correlated with slower cognitive decline in older adults, its role in POCD remains unclear. Here, IL-12p70 is identified as a significant mediator of therapeutic effect of electroacupuncture (EA) on POCD. EA at acupoints ST36, GV20, and GV24 significantly enhanced cognitive behaviors of POCD mice. IL-12p70, downregulated in POCD mice but rescued by EA treatment, is the cytokine closely associated with EA's therapeutic effect. Clinically, IL-12p70 is downregulated in older adults' serum post-surgery. Furthermore, IL-12p70 exerts a potent neuroprotective effect in both neuronal cell lines and primary hippocampal neurons. The PI3K-AKT-BCL2 axis enriched by in silico analysis is validated as the signaling mechanism underlying IL-12p70-induced neuroprotection. In vivo, beneficial effects of EA treatment on the activation of PI3K-AKT-BCL2 axis and POCD are reproduced by IL-12p70 administration but attenuated by IL-12p70 knockdown. The findings reveal a novel mechanism underlying the therapeutic effect of EA on POCD, demonstrating that IL-12p70 exerts a neuroprotective effect by activating PI3K-AKT-BCL2 axis in hippocampal neurons. The newly-discovered function and mechanism of IL-12p70 highlight its potential in treating cognitive disorders.

Mitochondrial modulation treating postoperative cognitive dysfunction neuroprotection via DRP1 inhibition by Mdivi1

This study investigated the role of mitochondrial dynamics in postoperative cognitive dysfunction (POCD) and assessed the therapeutic potential of mitochondrial modulation, particularly through the inhibition of dynamin-related protein 1 (DRP1) with Mdivi-1. Our findings indicated that DRP1 inhibition substantially mitigated neuroinflammation mediated by microglial cells, contributing to improved cognitive function in POCD models. The administration of Mdivi-1 led to a notable decrease in mitochondrial fission, reduced reactive oxygen species (ROS) production, and stabilization of mitochondrial membrane potential, all of which correlate with diminished neuroinflammation, as evidenced by lower NOD-like receptor family pyrin domain containing 3 (NLRP3)/ interleukin-1β (IL-1β) expression in microglial cells. Importantly, Mdivi-1 treatment was also found to enhance synaptic plasticity, increasing synaptic spine density in the hippocampal region of POCD mice. This improvement in mitochondrial health and synaptic integrity was paralleled by enhanced cognitive performance, as demonstrated in Y-maze tests. These results underscored the critical role of mitochondrial dynamics in the pathophysiology of POCD and suggested that targeting mitochondrial dysfunction, specifically through DRP1 inhibition, could be an effective approach for POCD treatment.

Evaluation of transcutaneous electrical acupoint stimulation for improving pain and cognitive function in elderly patients around the perioperative period of hip replacement surgery: A meta-analysis.

We aim to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS) in elderly patients around the perioperative period of hip replacement surgery. The China National Knowledge Infrastructure(CNKI), Wangfang Data, VIP database, SinoMed, PubMed, and Embase databases were searched for relevant publications until August 2024. All randomized controlled studies evaluating the efficacy and safety of TEAS in patients around the perioperative period of hip replacement surgery. We calculated pooled risk ratio (RR) with 95% CIs for binary outcomes and standardized mean difference (SMD) for continuous outcomes. The Cochrane's Risk of Bias Tool were used to evaluate the quality of studies. A total of 13 studies with 946 patients were included in this analysis. 1-day visual analogue scale (VAS) scores and 2-day VAS scores were significantly lower in the TEAS group compared to the control group (SMD: -0.78, 95% CI: -1.47, -0.09, P = 0.02 and SMD:-0.54, 95% CI:-1.00,-0.09,P = 0.02). Furthermore, 1-day mini-mental state examination (MMSE) scores and 3-day MMSE scores were significantly higher in the TEAS group compared to the control group (SMD: 1.60, 95% CI: 0.68, 2.51,P<0.001 and SMD:1.31, 95% CI:1.03,1.59,P<0.001), along with a lower postoperative cognitive dysfunction rate (RR: 0.55, 95% CI: 0.41, 0.73, P<0.001). Our meta-analysis demonstrated that TEAS significantly reduces pain and improves cognitive function in patients undergoing hip replacement surgery. Future studies should further investigate the optimal TEAS protocols to maximize these benefits across different population and surgical settings.

Effect of small dose esketamine on perioperative neurocognitive disorder and postoperative depressive symptoms in elderly patients undergoing major elective noncardiac surgery for malignant tumors: A randomized clinical trial.

Perioperative neurocognitive disorder and postoperative depressive symptoms are significant complications after surgery. Studies have indicated that esketamine possesses neuroprotective and antidepressant qualities. This trial included 209 patients aged 60 to 86 years undergoing tumor resection who received esketamine (Group E) or not (Group C) during and after surgery. In group E, patients were given an intravenous dose of 0.5 mg/kg of esketamine 10 minutes after induction of general anaesthesia. In addition, esketamine (2 mg/kg) in combination with sufentanil was used for PCIA during 48 hours postoperatively. On the other hand, saline was used as a substitute for esketamine in group C. Cognitive function was evaluated using neuropsychological tests and telephone interview for cognitive status-modified, and symptoms of depression were assessed using Hamilton Depression Rating Scale 17. Compared to Group C, patients in Group E exhibited lower rates of depressive symptoms at 3, 7, and 90 days post-surgery (53.9% vs 67.7%, 26.3% vs 47.9%, and 13.3% vs 28.4%). Group E also showed decreased time for Trail Making Test on days 7 and 90. However, there were no significant differences in the incidence of delirium 1 to 5 days post-surgery or cognitive impairment 90 days post-surgery between the 2 groups (12.1% vs 10.9% and 8.4% vs 9.7%). Intraoperative low-dose esketamine and postoperative low-dose esketamine combined with sufentanil for patient-controlled intravenous analgesia has been shown to improve postoperative analgesia, alleviate postoperative depressive symptoms, and aid in the recovery of social executive ability. However, this approach did not reduce the incidence of postoperative delirium or postoperative cognitive dysfunction.

Secukinumab ameliorates postoperative cognitive dysfunction in aged mice by reducing meningeal aggregation of γδT cell

Secukinumab ameliorates postoperative cognitive dysfunction in aged mice by reducing meningeal aggregation of γδT cell

The effect of Amantadine on recovery, postoperative cognitive dysfunction and pain after propofol anesthesia in mice

IntroductionPostoperative cognitive dysfunction (POCD) encompasses a spectrum of cognitive impairments following surgery, attributed to disruptions in brain homeostasis. The pathogenesis involves glutamate toxicity, GABA receptor dysfunction, and alterations in NMDA and AMPA receptors. This study aimed to investigate the impact of pre-anesthetic amantadine administration on postoperative recovery time, POCD, and stress-related pain levels when combined with propofol anesthesia. MethodsTwenty-four adult male BALB/C mice were divided into four groups: Control, Propofol, Amantadine, and Amantadine+Propofol. Amantadine and propofol doses were administered intraperitoneally based on previous literature. Recovery time, pain levels (assessed via tail pinch and hot plate tests), cognitive functions (evaluated through Morris Water Maze), and locomotor activity (measured via Open Field Test) were recorded. ResultsAmantadine administration significantly reduced recovery time from propofol anesthesia, prolonged pain perception, and preserved cognitive functions compared to propofol alone. The time spent in the target quadrant in the Morris Water Maze was significantly longer in groups receiving amantadine. Additionally, the distance covered until finding the platform was significantly shorter in the propofol-only group. DiscussionAmantadine's neuroprotective effects, attributed to its antagonistic action on glutamate and NMDA receptors, mitigate the detrimental effects of propofol on cognitive function and pain perception. This study highlights the potential of combining amantadine with propofol to enhance postoperative outcomes. ConclusionAmantadine administration before propofol anesthesia positively influenced postoperative recovery, cognitive function preservation, and stress-related pain perception in mice. These findings suggest a potential therapeutic strategy to mitigate POCD and pain associated with surgery.

Postoperative Electroacupuncture Boosts Cognitive Function Recovery after Laparotomy in Mice.

Postoperative cognitive dysfunction (POCD) is a common complication that affects memory, executive function, and processing speed postoperatively. The pathogenesis of POCD is linked to excessive neuroinflammation and pre-existing Alzheimer's disease (AD) pathology. Previous studies have shown that acupuncture improves cognition in the early phase of POCD. However, POCD can last for longer periods (up to weeks and years). The long-term effects of acupuncture are unknown. In this study, we hypothesized that electroacupuncture (EA) could reduce inflammation and cognitive dysfunction induced by laparotomy over a longer period. We characterized the effects of postoperative EA on cognitive changes and investigated the underlying molecular mechanisms in mice. Laparotomy was performed in 3-month-old mice followed by daily EA treatment for 2 weeks. Our data indicated that laparotomy induced prolonged impairment in memory and executive functions, which were mitigated by postoperative EA. EA also reduced tau phosphorylation and suppressed the activation of tau-related kinases and glia, with effects comparable to ibuprofen. These findings demonstrate the beneficial effects of EA in a mouse model of POCD, suggesting that EA's ability to suppress neuroinflammation may contribute to its protective effects. In conclusion, EA may be a viable non-pharmacological intervention for managing POCD in different phases of the medical condition.

The association of pre-operative biomarkers of endothelial dysfunction with the risk of post-operative neurocognitive disorders: results fromthe BioCog study.

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. 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. 19.8% of 788 patients developed POD; 10.1% of 537 patientshad POCDat 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 (adjustedodds ratio 0.55; 95% CI: 0.35-0.86). No further statistically significant results were found. Pre-operative concentrations of ED biomarkers werenot 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.

Neuroprotection of celastrol against postoperative cognitive dysfunction through dampening cGAS-STING signaling

Neuroinflammation is a central player in postoperative cognitive dysfunction (POCD), an intractable and highly confounding neurological complication with finite therapeutic options. Celastrol, a quinone methide triterpenoid, is a bioactive ingredient extracted from Tripterygium wilfordii with talented anti-inflammatory capacity. However, it is unclear whether celastrol can prevent anesthesia/surgery-evoked cognitive deficits in an inflammation-specific manner. The STING agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) was used to determine whether celastrol possesses neuroprotection dependent on the STING pathway in vivo and in vitro. Isoflurane and laparotomy triggered cGAS-STING activation, caspase-3/GSDME-dependent pyroptosis, and enhanced Iba-1 immunoreactivity. Celastrol improved cognitive performance and decreased the levels of cGAS, 2′3′-cGAMP, STING, NF-κB phosphorylation, Iba-1, TNF-α, IL-6, and IFN-β. Downregulation of cleaved caspase-3 and N-GSDME was observed in the hippocampus of POCD mice and HT22 cells after celastrol administration, accompanied by limited secretion of pyroptosis-pertinent pro-inflammatory cytokines IL-1β and IL-18. DMXAA neutralized the favorable influences of celastrol on cognitive function, as confirmed by the activation of the STING/caspase-3/GSDME axis. These findings implicate celastrol as a therapeutic agent for POCD through anti-inflammation and anti-pyroptosis.

MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis.

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. 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. 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. Our findings suggest that MEF2C may be a promising therapeutic target for POCD through its negative modulation of ferroptosis.

Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane-Induced Cognitive Dysfunction in Aged Mice.

Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice. We performed single-nucleus RNA sequencing (snRNA-seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane-induced alternation of glutamatergic synapses in the hippocampus of aged mice. This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice. Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

ID: 334677 Diminished Side-Port Aspiration and Post-Operative Cognitive Dysfunction Affecting the Diagnosis of Intrathecal Drug Delivery Complications

ID: 334677 Diminished Side-Port Aspiration and Post-Operative Cognitive Dysfunction Affecting the Diagnosis of Intrathecal Drug Delivery Complications