Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor ...Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.展开更多
The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed t...BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.展开更多
Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with atte...Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with attention deficit and memory reduction after surgery,among which serious patients are prone to personality change,which affects their social behavior ability.In the context of the current era,the cause of POCD is not clear,combined with the results of most studies,it is found that central nervous inflammation,is a key factor affecting POCD.From the perspective of central inflammation,this paper analyzes the relationship between central inflammation and POCD,and discusses the mechanism of action,aiming at effectively preventing and treating POCD and providing a reference for subsequent research in related fields.展开更多
BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)...BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.展开更多
BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical r...BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.展开更多
BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an imp...BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an important mechanism of DCD.Blocking calcium overload and restoring calcium homeostasis are key steps in treatment.Transient receptor potential melastatin 7(TRPM7)is a novel player in causing calcium overload.Our previous studies have shown that genetic silencing of TRPM7 in type 1 diabetic rats leads to significant improvements in cognitive function,but the specific mechanism remains unclear.Troxerutin,extracted from the flowers of Sophora japonica,is one of the derivatives of rutin and has been shown to have neuroprotective effects.However,its association with TRPM7 remains unclear.AIM To use animal and cellular models,we investigated whether TRPM7 mediated mitochondrial fission by upregulation of calcineurin(CaN)/dynamin-related protein 1(Drp1)ser637 in DCD,and whether Troxerutin improved DCD by inhibiting TRPM7-mediated mitochondrial division.METHODS In this study,we used db/db mice and hippocampal neuronal cell lines(HT22)treated with high-concentration glucose as our study subjects.We evaluated cognitive function using Morris water maze,novel object recognition tasks,and Nesting tests.We observed mitochondrial morphology using transmission electron microscopy and measured mitochondrial energy metabolism indicators using a spectrophotometer.We also detected mRNA and protein expression of TRPM7,CaN,p-Drp1^(ser637),caspase-3,B-cell lymphoma 2 associated X protein,and B-cell lymphoma 2 using quantitative real-time polymerase chain reaction,western blotting,and immunofluorescence.RESULTS In the db/db diabetic mice with cognitive dysfunction,as well as in hippocampal neurons exposed to high-concentration glucose,TRPM7 and CaN expression were upregulated,phosphorylated Drp1^(ser637)expression was downregulated,and mitochondrial fission was increased.By modulating(inhibiting or overexpressing)TRPM7,it was further validated that TRPM7 activates the CaN/Drp1^(ser637)pathway,resulting in an increase in mitochondrial fission and neuronal cell apoptosis.Troxerutin downregulated TRPM7/CaN/Drp1^(ser637),reduced mitochondrial fission,and improved DCD.CONCLUSION TRPM7 promotes mitochondrial fission via the CaN/Drp1^(ser637)pathway.Troxerutin improves mitochondrial function and reduces neuronal damage by inhibiting this pathway,suggesting TRPM7 as a potential therapeutic target for DCD.展开更多
Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a...Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a Food and Drug Administration(FDA)-approved cannabidiol(CBD),in improving brain function in a rat model of chronic GWI.Methods:Six months after exposure to low doses of GWI-related chemicals[pyridostigmine bromide,N,N-diethyl-meta-toluamide(DEET),and permethrin(PER)]along with moderate stress,rats with chronic GWI were administered either vehicle(VEH)or CBD(20 mg/kg,oral)for 16 weeks.Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory,object location memory,pattern separation,and sucrose preference.The effect of CBD on hyperalgesia was also examined.The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.Results:GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia,whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia.Additionally,CBD treatment alleviated hyperalgesia in GWI rats.Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription(JAK/STAT)signaling.Furthermore,there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis.In contrast,the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling,normalized concentrations of proinflammatory cytokines and oxidative stress markers,and improved neurogenesis.Notably,CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.Conclusions:The use of an FDA-approved CBD(Epidiolex®)has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI.Importantly,the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this s...Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.展开更多
This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly imp...This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.展开更多
Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflamm...Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.展开更多
The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review...The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics.The second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.展开更多
OBJECTIVE: To investigate neuropsychological features of post-stroke cognitive impairment with no dementia(PSCIND) patients with different Traditional Chinese Medicine(TCM) syndromes.METHODS: We recruited 50 patients ...OBJECTIVE: To investigate neuropsychological features of post-stroke cognitive impairment with no dementia(PSCIND) patients with different Traditional Chinese Medicine(TCM) syndromes.METHODS: We recruited 50 patients with PSCIND between April 2012 and March 2013. Patients were divided into different groups according to TCM classifications. Patients were assessed using neuropsychological tests, including cognitive screening(mini-mental state examination), memory testing (auditory verbal learning test), executive/attention[shape trails test, stroop color-word test(SCWT),reading the mind in the eyes test, the digit ordering test-A(DOT-A), and symbol digit modalities test], language(action naming test, Boston naming test, famous face test, similarity test, and verbal fluency test), and visuospatial functioning [complex figure test(CFT)].RESULTS: We found no significant differences between patients with and without a diagnosis of turbid phlegm blocking the upper orifices on neuropsychological test performance. Patients diagnosed with upper hyperactivity of liver Yang syndrome scored significantly lower on the SCWT-C executive test and the CFT-delayed recall memory test. Patients with excess syndrome scored significantly lower on the SCWT-C executive test, and significantly higher on the DOT-A executive test.CONCLUSION: Neuropsychological characteristics differ between PSCIND patients with different TCM classifications.展开更多
Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-...Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association （ASA） physical status being at Grades Ⅰ-Ⅲ. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction （t1）, at the beginning of OLV （t2）, and at the time of OLV 30 min （t3）, OLV 60 min （t4）, the end of OLV （t5）, and the end of surgery （t6） were recorded. The intraoperative average of rSO2 （ rSO2 ）, the intraoperative minimum value of rSO2 （rSO2, rn=n）, and the reduced maximum percentage of rSO2 （rSO2, %max） when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. Results： A total of 14 patients （28%） in the 50 cases suffered from POCD. The values of mini-mental state examination （MMSE）, the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation （P〈0.05）. The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group （P〈0.05）. The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at tl （P〈0.05）. The values of rSO2, %max in the POCD group were significantly higher than those in the non-POCD group （P〈0.05）. When the value of rSO2, %max is more than 10.1%, it may act as an early warning index for cognitive function changes, Conclusions： POCD after OLV may be associated with a decline in rSO2.展开更多
Objective:To observe the clinical effect on post-stroke cognitive impairment(PSCI) treated by acupuncture at the acupoints composed in accordance with the "four seas theory".Methods:A total of 70 patients wi...Objective:To observe the clinical effect on post-stroke cognitive impairment(PSCI) treated by acupuncture at the acupoints composed in accordance with the "four seas theory".Methods:A total of 70 patients with PSCI were randomly divided into a treatment group(n=35) and a control group(n=35).In the control group,conventional basic treatment and rehabilitation training were adopted,while in the treatment group,on the base of the treatment as the control group,acupuncture was applied at the acupoints composed in accordance with "four seas theory",lasting 8 weeks.The scores of mini-mental state examination(MMSE) and the instantaneous memory,the scores of Montreal cognitive assessment(MoCA) and the delayed memory,the score of kidney essence insufficiency in syndrome differentiation scale of vascular dementia(SDSVD),event-related potentials(ERP) P300 and clinical therapeutic effect were compared in the patients between two groups before and after treatment separately.Results:After treatment,MMSE score and the score of instantaneous memory were higher than the results before treatment in either group respectively(all P <0.05),in which,MMSE score in the treatment group was higher than that in the control group(P <0.05).After treatment,MoCA score and the score of delay recall were higher than the results before treatment in either group(all P <0.05),in which,MoCA score in the treatment group was higher than that of the control group(P <0.05).After treatment,the score of SDSVD was lower than that before treatment in either group(both P <0.05),in which SDSVD score in the treatment group were lower than the control group(P <0.05).There were no statistical changes in P300 latency and wave amplitude in the patients of the control group after treatment(both P> 0.05).However,in the treatment group,P300 latency was reduced and the wave amplitude was increased after treatment(both P <0.05).The total effective rate was 88.57% in the treatment group,higher than 71.43% in the control group(P <0.05).Conclusion:Acupuncture at the acupoints composed on the base of the "four seas theory" effectively improves the cognitive function and traditional Chinese medicine syndrome scores in PSCI patients.This therapy is of great value in clinic in the future.展开更多
Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(N...Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.展开更多
Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats whic...Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.展开更多
Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancre...Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.展开更多
基金supported by the National Natural Science Foundation of China,No.81673263(to YHZ)Ministry of Science and Technology of China,No.2016YFC1307300(to YHZ)a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(to YHZ)
文摘Stroke is the leading cause of death and long-term disability worldwide,and cognitive impairment and dementia are major complications of ischemic stroke.Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies.However,the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results.This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months.Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke.According to the MMSE score,308 patients (52.9%) had post-stroke cognitive dysfunction.After adjusting for potential confounding factors,the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98),compared with the lowest quartile.The correlation between serum CysC and cognitive dysfunction was modified by renal function status.We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044),but not in those with abnormal renal function.Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke,especially in those with normal renal function.The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction,and could be used to treat post-stroke cognitive dysfunction.The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No.2012-02) on December 30,2012,and was registered at ClinicalTrials.gov (identifier No.NCT01840072) on April 25,2013.
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金Supported by the Research Fund of Qiannan Medical College for Nationalities,No.Qnyz202222.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.
基金Jiangsu University Student Innovation and Entrepreneurship Project,“Study on the Mechanism of TLR4-mediated Central Inflammation Induced by Glial Cell Activation to POCD”(Project No.:202313980027Y)。
文摘Postoperative cognitive dysfunction is a typical complication,which can be referred to as POCD.This complication is common in elderly patients.Among them,POCD is mainly manifested in the function of patients with attention deficit and memory reduction after surgery,among which serious patients are prone to personality change,which affects their social behavior ability.In the context of the current era,the cause of POCD is not clear,combined with the results of most studies,it is found that central nervous inflammation,is a key factor affecting POCD.From the perspective of central inflammation,this paper analyzes the relationship between central inflammation and POCD,and discusses the mechanism of action,aiming at effectively preventing and treating POCD and providing a reference for subsequent research in related fields.
基金Supported by the National Natural Science Foundation of China,No.82300894.
文摘BACKGROUND Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function,which is linked to oligodendrocyte dysfunction.The voltage-gated proton channel 1(Hv1)is important for the cellular proton extrusion machinery.However,its role in regulating diabetesinduced cognitive dysfunction is unclear.AIM To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms,focusing on neuroinflammation,oligodendrocyte apoptosis,and axonal demyelination.METHODS A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice.Hv1 knockout(KO)and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence.Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination wasanalyzed using electron microscopy.RESULTSHv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitiveimpairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, includinginterleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelinthickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO.CONCLUSIONHv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelinintegrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline andassociated complications.
文摘BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.
基金Supported by the Natural Science Foundation of Hebei Province,No.H2021206187 and No.H2021206452.
文摘BACKGROUND Diabetic cognitive dysfunction(DCD)is one of the chronic complications of diabetes,but its mechanism is currently unknown.Studies have shown that mitochondrial fission mediated by calcium overload is an important mechanism of DCD.Blocking calcium overload and restoring calcium homeostasis are key steps in treatment.Transient receptor potential melastatin 7(TRPM7)is a novel player in causing calcium overload.Our previous studies have shown that genetic silencing of TRPM7 in type 1 diabetic rats leads to significant improvements in cognitive function,but the specific mechanism remains unclear.Troxerutin,extracted from the flowers of Sophora japonica,is one of the derivatives of rutin and has been shown to have neuroprotective effects.However,its association with TRPM7 remains unclear.AIM To use animal and cellular models,we investigated whether TRPM7 mediated mitochondrial fission by upregulation of calcineurin(CaN)/dynamin-related protein 1(Drp1)ser637 in DCD,and whether Troxerutin improved DCD by inhibiting TRPM7-mediated mitochondrial division.METHODS In this study,we used db/db mice and hippocampal neuronal cell lines(HT22)treated with high-concentration glucose as our study subjects.We evaluated cognitive function using Morris water maze,novel object recognition tasks,and Nesting tests.We observed mitochondrial morphology using transmission electron microscopy and measured mitochondrial energy metabolism indicators using a spectrophotometer.We also detected mRNA and protein expression of TRPM7,CaN,p-Drp1^(ser637),caspase-3,B-cell lymphoma 2 associated X protein,and B-cell lymphoma 2 using quantitative real-time polymerase chain reaction,western blotting,and immunofluorescence.RESULTS In the db/db diabetic mice with cognitive dysfunction,as well as in hippocampal neurons exposed to high-concentration glucose,TRPM7 and CaN expression were upregulated,phosphorylated Drp1^(ser637)expression was downregulated,and mitochondrial fission was increased.By modulating(inhibiting or overexpressing)TRPM7,it was further validated that TRPM7 activates the CaN/Drp1^(ser637)pathway,resulting in an increase in mitochondrial fission and neuronal cell apoptosis.Troxerutin downregulated TRPM7/CaN/Drp1^(ser637),reduced mitochondrial fission,and improved DCD.CONCLUSION TRPM7 promotes mitochondrial fission via the CaN/Drp1^(ser637)pathway.Troxerutin improves mitochondrial function and reduces neuronal damage by inhibiting this pathway,suggesting TRPM7 as a potential therapeutic target for DCD.
基金supported by grants from Jazz Pharmaceuticals Inc.the Texas A&M University of School of Medicine to AKS
文摘Background:Chronic Gulf War Illness(GWI)is characterized by cognitive and mood impairments,as well as persistent neuroinflammation and oxidative stress.This study aimed to investigate the efficacy of Epidiolex®,a Food and Drug Administration(FDA)-approved cannabidiol(CBD),in improving brain function in a rat model of chronic GWI.Methods:Six months after exposure to low doses of GWI-related chemicals[pyridostigmine bromide,N,N-diethyl-meta-toluamide(DEET),and permethrin(PER)]along with moderate stress,rats with chronic GWI were administered either vehicle(VEH)or CBD(20 mg/kg,oral)for 16 weeks.Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory,object location memory,pattern separation,and sucrose preference.The effect of CBD on hyperalgesia was also examined.The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.Results:GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia,whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia.Additionally,CBD treatment alleviated hyperalgesia in GWI rats.Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription(JAK/STAT)signaling.Furthermore,there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis.In contrast,the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling,normalized concentrations of proinflammatory cytokines and oxidative stress markers,and improved neurogenesis.Notably,CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.Conclusions:The use of an FDA-approved CBD(Epidiolex®)has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI.Importantly,the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by the National Natural Science Foundation of China,No.81473740,81673627,81673717(to QW)Guangzhou Science Technology and Innovation Commission Technology Research Projects,China,No.2018050100(to QW)+3 种基金the Foundation for Characteristic Innovation of Educational Commission of Guangdong Province,China,Grant No.2016KTSCX011(to SHF)the Open Tending Project for Construction of High-Level University,Guangzhou University of Chinese Medicine,China,No.34 and 118,2017(to SHF)the Technology Platform of Clinical Trials on New Traditional Medicine,China,No.2012ZX09303009-003(to WXL)the Technology Platform of Clinical Evaluation on New Traditional Medicine,China,No.2008ZX09312-021(to WXL)
文摘Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.
基金supported by the National Natural Science Foundation of China,No.30871306
文摘This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.
文摘Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.
基金This review was supported by the National Key R&D Program of China(2016YFC1306900)the National Natural Science Foundation of China(81622018)an Innovation Driven Project of Central South University(2020CX018).
文摘The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics.The second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.
基金Traditional Chinese Medicine Three-Year Action Plan(21.24.03)
文摘OBJECTIVE: To investigate neuropsychological features of post-stroke cognitive impairment with no dementia(PSCIND) patients with different Traditional Chinese Medicine(TCM) syndromes.METHODS: We recruited 50 patients with PSCIND between April 2012 and March 2013. Patients were divided into different groups according to TCM classifications. Patients were assessed using neuropsychological tests, including cognitive screening(mini-mental state examination), memory testing (auditory verbal learning test), executive/attention[shape trails test, stroop color-word test(SCWT),reading the mind in the eyes test, the digit ordering test-A(DOT-A), and symbol digit modalities test], language(action naming test, Boston naming test, famous face test, similarity test, and verbal fluency test), and visuospatial functioning [complex figure test(CFT)].RESULTS: We found no significant differences between patients with and without a diagnosis of turbid phlegm blocking the upper orifices on neuropsychological test performance. Patients diagnosed with upper hyperactivity of liver Yang syndrome scored significantly lower on the SCWT-C executive test and the CFT-delayed recall memory test. Patients with excess syndrome scored significantly lower on the SCWT-C executive test, and significantly higher on the DOT-A executive test.CONCLUSION: Neuropsychological characteristics differ between PSCIND patients with different TCM classifications.
基金supported by the Foundation of Shandong Science and Technology Project(No.2011YD18070),China
文摘Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association （ASA） physical status being at Grades Ⅰ-Ⅲ. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction （t1）, at the beginning of OLV （t2）, and at the time of OLV 30 min （t3）, OLV 60 min （t4）, the end of OLV （t5）, and the end of surgery （t6） were recorded. The intraoperative average of rSO2 （ rSO2 ）, the intraoperative minimum value of rSO2 （rSO2, rn=n）, and the reduced maximum percentage of rSO2 （rSO2, %max） when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. Results： A total of 14 patients （28%） in the 50 cases suffered from POCD. The values of mini-mental state examination （MMSE）, the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation （P〈0.05）. The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group （P〈0.05）. The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at tl （P〈0.05）. The values of rSO2, %max in the POCD group were significantly higher than those in the non-POCD group （P〈0.05）. When the value of rSO2, %max is more than 10.1%, it may act as an early warning index for cognitive function changes, Conclusions： POCD after OLV may be associated with a decline in rSO2.
文摘Objective:To observe the clinical effect on post-stroke cognitive impairment(PSCI) treated by acupuncture at the acupoints composed in accordance with the "four seas theory".Methods:A total of 70 patients with PSCI were randomly divided into a treatment group(n=35) and a control group(n=35).In the control group,conventional basic treatment and rehabilitation training were adopted,while in the treatment group,on the base of the treatment as the control group,acupuncture was applied at the acupoints composed in accordance with "four seas theory",lasting 8 weeks.The scores of mini-mental state examination(MMSE) and the instantaneous memory,the scores of Montreal cognitive assessment(MoCA) and the delayed memory,the score of kidney essence insufficiency in syndrome differentiation scale of vascular dementia(SDSVD),event-related potentials(ERP) P300 and clinical therapeutic effect were compared in the patients between two groups before and after treatment separately.Results:After treatment,MMSE score and the score of instantaneous memory were higher than the results before treatment in either group respectively(all P <0.05),in which,MMSE score in the treatment group was higher than that in the control group(P <0.05).After treatment,MoCA score and the score of delay recall were higher than the results before treatment in either group(all P <0.05),in which,MoCA score in the treatment group was higher than that of the control group(P <0.05).After treatment,the score of SDSVD was lower than that before treatment in either group(both P <0.05),in which SDSVD score in the treatment group were lower than the control group(P <0.05).There were no statistical changes in P300 latency and wave amplitude in the patients of the control group after treatment(both P> 0.05).However,in the treatment group,P300 latency was reduced and the wave amplitude was increased after treatment(both P <0.05).The total effective rate was 88.57% in the treatment group,higher than 71.43% in the control group(P <0.05).Conclusion:Acupuncture at the acupoints composed on the base of the "four seas theory" effectively improves the cognitive function and traditional Chinese medicine syndrome scores in PSCI patients.This therapy is of great value in clinic in the future.
基金supported by the National Natural Science Foundation of China(81872654,81703264)Fundamental Research Funds of Shandong University(2016JC020),ChinaNatural Science Foundation of Shandong Province(ZR2017MH002),China
文摘Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
基金supported by grants from the National Natural Science Foundation of China(No.81271233,No.81200880,No.31240030)
文摘Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.
基金Project supported by the Shandong Science and Technology Development Project(No.2011YD18070),China
文摘Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.
