Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Impact of propofol and sevoflurane anesthesia on cognition and emotion in gastric cancer patients undergoing radical resection

BACKGROUND Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer.However,there is a debate concerning their differential effects on cognitive function,anxiety,and depression in patients undergoing this procedure.AIM To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function,anxiety,depression,and organ function in patients undergoing radical resection of gastric cancer.METHODS A total of 80 patients were involved in this research.The subjects were divided into two groups:Propofol group and sevoflurane group.The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment(LOTCA),and anxiety and depression were assessed with the aid of the self-rating anxiety scale(SAS)and self-rating depression scale(SDS).Hemodynamic indicators,oxidative stress levels,and pulmonary function were also measured.RESULTS The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group.Additionally,the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group.The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group.Moreover,the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group.CONCLUSION Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer.Propofol anesthesia has a minimal effect on patients'pulmonary function,consequently enhancing their postoperative recovery.Sevoflurane anesthesia causes less impairment on patients'cognitive function and mitigates negative emotions,leading to an improved postoperative mental state.Therefore,the selection of anesthetic agents should be based on the individual patient's specific circumstances.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients

BACKGROUND The pathogenesis of cognitive impairment in schizophrenia(SCZ)remains unclear.Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor(BDNF)levels play a crucial role in the psychopathology of SCZ.However,their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated.AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ.METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ(SCZ group)and 80 healthy controls(HCs group)at the Huzhou Third Municipal Hospital between August 2021 and September 2023.ELISA was employed to measure the serum levels of interleukin(IL)-1β,IL-4,IL-6,IL-10,and BDNF.The Chinese brief cognitive test(C-BCT)and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms.RESULTS Compared to the HC group,the SCZ group exhibited elevated IL-1βand IL-6 levels,decreased BDNF levels,and reduced C-BCT scores(all P<0.001).In SCZ,BDNF was negatively correlated with IL-6(r=-0.324,P<0.05).Information processing speed was negatively correlated with IL-6(r=-0.315,P<0.05)and positively with BDNF(r=0.290,P<0.05);attention,working memory,comprehensive ability,and executive function were negatively correlated with IL-1βand IL-6(all P<0.05)and positively with BDNF(all P<0.05).Multiple regression analysis showed IL-6 influenced C-BCT dimensions(β=-0.218 to-0.327,all P<0.05);attention and executive ability were influenced by IL-1β(β=-0.199 to-0.261,all P<0.05);comprehensive executive ability was influenced by BDNF(β=0.209,P<0.05).CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

Outcomes of the effect of exercise on cognitive function in patients with depression:A meta-analysis

BACKGROUND Major depressive disorder is a common mental disorder,characterized by a high rate of suicide and recurrence,which is frequently accompanied by cognitive impairments,particularly in executive function,memory,attention,and infor-mation processing speed.As such,improving the cognitive function in patients with depression and enhancing their quality of life are urgent issues.AIM To perform a systematic review and meta-analysis of the effects of exercise on cognitive function in patients with depression.METHODS The PubMed,Web of Science,Cochrane Library,Embase,China National Knowledge Infrastructure,Wanfang Medical,VIP,and Biomedical Databases for randomized controlled trials(RCTs)databases were searched(from inception to October 19,2023)for studies investigating improvements in cognitive function in patients with depression through exercise.Tools recommended by the Cochrane Handbook for RCT evaluation,and GRADEpro and Stata17 software,were employed for risk of bias assessment,evidence grading,forest plot construction,subgroup and sensitivity analyses,and assessment of publication bias.RESULTS Seventeen RCTs(1173 patients with depression)were included.Exercise had a small but significant positive effect on attention,with an effect size of 0.21,95%CI:0.07-0.34,P<0.01.Specifically,aerobic exercise regimens of 30-60 minute/session,thrice a week,at moderate intensity,and sustained over 3-12 weeks,were associated with the most pronounced benefits(P<0.05),with effect sizes for executive function,memory,and information processing speed of 0.11,95%CI:-0.11-0.32,P=0.34;0.08,95%CI:0.00-0.16,P=0.05;and 0.14,95%CI:0.04-0.25,P=0.01,respectively.The evidence levels for attention,information processing speed,and memory were rated as'low,’whereas that for executive function was rated as'very low’.CONCLUSION Exercise could improve attention and information-processing speed in patients with depression,although improvements in executive function and memory are not significant.

Relationship between intracranial pressure and neurocognitive function among older adults after radical resection of rectal cancer

BACKGROUND Older patients are prone to postoperative cognitive decline after laparoscopic rectal cancer surgery,which may be associated with increased intraoperative intracranial pressure(ICP).This study investigated the correlation between intra-operative ICP changes,as indicated by measurements of the optic nerve sheath diameter(ONSD)using ultrasonography,and subsequent cognitive function to provide better patient care.AIM To evaluate changes in ICP and associated postoperative neurocognition in older adults after laparoscopic radical resection for rectal cancer.METHODS We included 140 patients who visited the Mianyang Central Hospital for malig-nant rectal tumors,measured their ONSDs before surgery and 30 and 60 minutes after the Trendelenburg position during surgery,and evaluated the patients’cog-nitive function 1 day before surgery and 1,4,and 7 days after surgery.The Mini-Mental State Examination(MMSE)and confusion assessment method(CAM)scores of the patients with different ONSDs were compared at different times after surgery.RESULTS In patients with an ONSD greater than 5.00 mm(group A1),the MMSE scores at 1 day and 4 days after surgery were significantly lower than those of patients with an ONSD less than or equal to 4.00 mm(group A2)(P<0.05).The CAM scores of group A1 were significantly higher than those of group A2(P<0.05).The MMSE scores of group A1 on days 1 and 4 after surgery were significantly lower than those 1 day before and 7 days after surgery(P<0.05),while the CAM scores 1 day and 4 days after surgery were significantly higher than those 1 day before and 7 days after surgery.CONCLUSION Decline in cognitive function among older adults after the procedure may be related to intracranial hypertension during surgery.

Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

BACKGROUND Patients with schizophrenia may have various disease manifestations,most of which gradually tend toward incurable chronic decline,leading to mental disability.The basic symptoms of the disease can impair social function,whereas long-term hospitalization produces hospitalization syndrome,causing serious damage to social function.AIM To investigate the effects of Computerized Cognitive Remediation Therapy(CCRT)on cognitive and social functioning in patients with chronic schizophrenia.METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed.They were divided into an intervention group(60 cases treated with CCRT combined with conventional medication)and a control group(60 cases treated with conventional medication).After treatment,effects on cognitive function and social roles were observed in both groups.The Positive and Negative Syndrome Scale(PANSS)was used to assess the patients'psychiatric symptoms.The Wisconsin Card Sorting Test(WCST)was used to assess the patients'cognitive functioning,and the Social Functioning Scale for Psychiatric Inpatients(SSPI)was used to assess the social functioning of the inpatient psychiatric patients.RESULTS No significant differences were observed in the PANSS,WCST,and SSPI intergroup scores before treatment(P>0.05).After 2,4,and 6 wk of therapy,general psychopathological factors,positive symptoms,negative symptoms,and total PANSS scores of PANSS in the intervention group were lower than in the control group(P<0.05).After 2,4,and 6 wk of treatment,the number of false responses,number of persistent bugs,and total responses in the WCST were significantly lower in the intervention group than in the control group(P<0.05),and the amount of completed classification was significantly higher than in the control group(P<0.05).After 2,4,and 6 wk of therapy,the SSPI scores were significantly greater than those of the controls(P<0.05).After 6 wk of treatment,the efficacy rates of the control and intervention groups were 81.67%and 91.67%,respectively.The curative effect in the intervention group was significantly higher than that in the control group(P<0.05).CONCLUSION CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.

Abnormalities of electroencephalography microstates in patients with depression and their association with cognitive function

BACKGROUND A growing number of recent studies have explored underlying activity in the brain by measuring electroencephalography(EEG)in people with depression.However,the consistency of findings on EEG microstates in patients with depression is poor,and few studies have reported the relationship between EEG microstates,cognitive scales,and depression severity scales.AIM To investigate the EEG microstate characteristics of patients with depression and their association with cognitive functions.METHODS A total of 24 patients diagnosed with depression and 32 healthy controls were included in this study using the Structured Clinical Interview for Disease for The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.We collected information relating to demographic and clinical characteristics,as well as data from the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS;Chinese version)and EEG.RESULTS Compared with the controls,the duration,occurrence,and contribution of microstate C were significantly higher[depression(DEP):Duration 84.58±24.35,occurrence 3.72±0.56,contribution 30.39±8.59;CON:Duration 72.77±10.23,occurrence 3.41±0.36,contribution 24.46±4.66;Duration F=6.02,P=0.049;Occurrence F=6.19,P=0.049;Contribution F=10.82,P=0.011]while the duration,occurrence,and contribution of microstate D were significantly lower(DEP:Duration 70.00±15.92,occurrence 3.18±0.71,contribution 22.48±8.12;CON:Duration 85.46±10.23,occurrence 3.54±0.41,contribution 28.25±5.85;Duration F=19.18,P<0.001;Occurrence F=5.79,P=0.050;Contribution F=9.41,P=0.013)in patients with depression.A positive correlation was observed between the visuospatial/constructional scores of the RBANS scale and the transition probability of microstate class C to B(r=0.405,P=0.049).CONCLUSION EEG microstate,especially C and D,is a possible biomarker in depression.Patients with depression had a more frequent transition from microstate C to B,which may relate to more negative rumination and visual processing.

Associations between residence and cognitive function among Chinese older adults: the mediating role of leisure activity

Background:Cognitive function is a current research hotspot,residence may be related to differences in cognitive function,and the mediating role of leisure activities are limited in Chinese research.This study used leisure activities as a mediating variable to investigate the mediating role of leisure activity between place of residence(city-town-rural)and cognitive function among Chinese older,this is where the innovation of the article comes in.Methods:Using cross-sectional data from the 2018 Chinese Longitudinal Healthy Longevity Survey,Pearson correlation analyses were employed to examine the relationships among various indicators.Mediation analyses were conducted using the SPSS PROCESS macro program,version 3.5,written by Hayes,to explore the mediating effects of leisure activity between place of residence and cognitive function in older adults.Results:A total of 10955 older adults were included in this study,with a mean age of(84.23±11.57)years.Among them,2739(24.8%)lived in the city,3627(33.1%)in town,and 4615(42.1%)in rural areas;their leisure activity score was(5.34±3.77),and their cognitive function score was(24.69±6.65).Place of residence,leisure activities,and cognitive function were significantly correlated(P<0.01).Using city as a reference,place of residence is negatively associated with cognitive function,and place of residence not only had a direct effect on cognitive function in older adults:town-cognitive function(effect=–0.399;95%confidence interval(CI)=(–0.685,–0.113));rural-cognitive function(effect=–0.42;95%CI=(–0.698,–0.141)).There were also indirect effects on cognitive function through the pathway of leisure activity:town-leisure activity-cognitive function(effect=–0.17;95%CI=(–0.246,–0.1)),rural-leisure activity-cognitive function(effect=–0.199;95%CI=(–0.272,–0.13)).Conclusion:Leisure activities play a partially mediating role between the impact of place of residence and cognitive function in Chinese older adults,and it is vital to pay attention to the impact of place of residence on the cognitive function of older adults in various aspects,and to increase the participation rate of older adults in leisure activities,which is beneficial to the prevention of cognitive decline and the protection of older adult’s physical and mental health.

Clinical Study on the Effect of Continuity of Care in CICU on Improving Cognitive Function and Psychological State in Patients with Heart Failure

Objective:To analyze the effect of continuity of care in the cardiac intensive care unit(CICU)on improving cognitive function and psychological state in patients with heart failure(HF).Methods:A total of 112 chronic HF patients admitted to the CICU of Xuzhou Traditional Chinese Medicine Hospital from July 2022 to August 2024 were selected and randomly divided into two groups using the red and blue ball method:a control group(n=56)and a study group(n=56).The control group received routine CICU nursing management,while the study group received routine CICU nursing combined with continuity of care management.Cognitive function(using the Montreal Cognitive Assessment,MoCA),psychological state(using the Self-Rating Depression Scale,SDS,and Self-Rating Anxiety Scale,SAS),and quality of life(using the Minnesota Living with Heart Failure Questionnaire,MLHFQ)were compared between the two groups.Results:After the intervention,the cognitive function scores of the study group were significantly higher than those of the control group(P<0.05).The SDS and SAS scores of the study group were significantly lower than those of the control group after the intervention(P<0.05).The quality of life in the study group was also significantly better than in the control group(P<0.05).Conclusion:CICU continuity of care can effectively improve cognitive function and psychological state in patients with HF,while also enhancing their quality of life.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction

AIM To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha was examined. RESULTS FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating proinflammatory factors such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. CONCLUSION FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia:A systematic review and network meta-analysis

Background:Exercise is a promising nonpharmacological therapy for cognitive dysfunction,but it is unclear which type of exercise is most effective.The objective of this study was to compare and rank the effectiveness of various exercise interventions on cognitive function in patients with mild cognitive impairment(MCI)or dementia and to examine the effects of exercise on the symptoms relevant to cognitive impairment.Methods:We searched PubMed,Web of Science,Embase,Cochrane Central Register of Controlled Trials,SPORTDiscus,and PsycInfo through September 2019 and included randomized controlled trials that examined the effectiveness of exercise interventions in patients with MCI or dementia.Primary outcomes included global cognition,executive cognition,and memory cognition.Secondary outcomes included activities of daily living,neuropsychiatric symptoms,and quality of life.Pairwise analyses and network meta-analyses were performed using a random effects model.Results:A total of 73 articles from 71 trials with 5606 participants were included.All types of exercise were effective in increasing or maintaining global cognition,and resistance exercise had the highest probability of being the most effective intervention in slowing the decrease in global cognition(standard mean difference(SMD)=1.05,95%confidence interval(95%CI):0.56-1.54),executive function(SMD=0.85,95%CI:0.21-1.49),and memory function(SMD=0.32,95%CI:0.01-0.63)in patients with cognitive dysfunction.Subgroup analyses for patients with MCI revealed different effects,and multicomponent exercise was most likely to be the optimal exercise therapy for preventing the decline of global cognition(SMD=0.99,95%CI:0.44-1.54)and executive function(SMD=0.72,95%CI:0.06-1.38).However,only resistance exercise showed significant effects on memory function for patients with MCI(SMD=0.35,95%CI:0.01-0.69).Exercise interventions also showed various effects on the secondary outcomes.Conclusion:Resistance exercise has the highest probability of being the optimal exercise type for slowing cognitive declin e in patients withcognitive dysfunction,especially in patients with dementia.Multicomponent exercise tends to be most effective in protecting global cognition and executive function in patients with MCI.

Hippocampal insulin resistance and the Sirtuin 1 signaling pathway in diabetes-induced cognitive dysfunction

In the peripheral nervous system,the activation of Sirtuin 1 can improve insulin resistance;however,the role played by Sirtuin 1 in the central nervous system remains unknown.In this study,rat models of diabetes mellitus were generated by a single injection of streptozotocin.At 8 weeks after streptozotocin injection,the Morris water maze test and western blot assays confirmed that the diabetic model rats had learning and memory deficits,insulin resistance,and Sirtuin 1 expression could be detected in the hippocampus.Insulin and the insulin receptor inhibitor S961 were intranasally administered to investigate the regulatory effects of insulin signaling on Sirtuin 1.The results showed that insulin administration improved the impaired cognitive function of diabetic model rats and increased the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1 in the hippocampus.Conversely,S961 administration resulted in more severe cognitive dysfunction and reduced the expression levels of phosphorylated insulin receptor,phosphorylated insulin receptor substrate 1,and Sirtuin 1.The Sirtuin 1 activator SRT2104 and the inhibitor Sirtinol were injected into the lateral ventricle,which revealed that the activation of Sirtuin 1 increased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor.Hippocampal dendritic length and spine density also increased in response to Sirtuin 1 activation.In contrast,Sirtinol decreased the expression levels of target of rapamycin complex 1,phosphorylated cAMP-response elementbinding protein,and brain-derived neurotrophic factor and damaged the dendritic structure.These findings suggest that the Sirtuin 1 signaling pathway plays an important role in the development of insulin resistance-related cognitive deficits in diabetic rats.This study was approved by the Animal Ethics Welfare Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine(approval No.ZYFY201811207)in November 2018.

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

Influences of Microwave on the Cognitive Function of Chickling and the Gene Expression of NMDA Receptor Subunit

[Objective] The research aimed to study the effects of microwave on the chick embryo development and the cognitive function of chickling. [Method] The microwave which was transmitted by the permatron and was 2 450 MHz was used to simulate the microwave radiation source to radiate the hatching eggs until the chickling was hatched out. The disposable passive avoidance learning and RT-PCR were respectively used to detect the influences of microwave on the cognitive function of chickling and the expression amounts of NMDA receptor NR1 and NR2 subunits. [Result] After the microwave radiation,the avoidance rate of exposed group was significantly lower than that in the control group. Especially the avoidance rate of highest radiation intensity group was extremely significantly lower than that in the control group. Meanwhile,the body weights of two groups of chickling in the exposed group increased,and the hatching time in one group increased. Via RT-PCR analysis,the expression amount of NR2 subunit increased on the 10th day and the 15th day. The expression amount of NR1 subunit only decreased on the 15th day. [Conclusion] The microwave had the certain influence on the individual development. By changing the structure composition and function of NMDA receptor in the endbrain,the microwave made the self-regulation ability of chickling decline,which had the certain damage on the cognitive function.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Extremely low frequency electromagnetic fields promote cognitive function and hippocampal neurogenesis of rats with cerebral ischemia

Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this study, we established rat models of middle cerebral artery occlusion/reperfusion.One day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive days.Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats.The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats.The number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats.Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats.These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway.The study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.

Effects of Lipoxin A4 Pretreatment on Cognitive Function of Aged Rats after Global Cerebral Ischemia Reperfusion

The aim of the present study was to investigate the effect of lipoxin A4 （LXA4） pretreatment on cognitive function of aged rats after global cerebral ischemia reperfusion, and to explore its possible mechanism. Thirty-six aged male Sprague-Dawley rats were randomly divided into three groups （n=12 each）： sham-operation group （S group）, global cerebral ischemia reperfusion group （I/R group） and LXA4-pretreatment group （L group）. The rat model of global cerebral ischemia reperfusion was established by occlusion of the bilateral common carotid artery with hypotension. The cognitive function of rats was determined by a step-down type passive avoidance test and Morris Water Maze test on the third day after reperfusion. Rats were sacrificed after Water Maze test and the pathological changes ofhippocampal CA1 region were observed and the related inflammatory mediators were determined. As compared with S group, the escape latency in I/R group was prolonged from the first day to the fifth day, while that in L group was prolonged from the first day to the third day. The retention time in I/R group and L group in the first quadrant was shortened. The reaction time, frequency of reaction mistake and frequency of escape mistake in I/R group increased, and the latent period shortened. The frequency of escape mistake in L group increased, and the damage in the hippocampal CAI region of I/R group and L group was obvious. The levels of S-10013, TNF-α, IL-1β, IL-10 and NF-κB in I/R group and L group increased. As compared with I/R group, the escape latency in L group was shortened from the first day to the fifth day, and the retention time in the first quadrant prolonged. The reaction time, frequency of reaction mistake and frequency of escape mistake in L group decreased, and the latent period prolonged. The damage in the hippocampal CA1 region of L group was alleviated as well. The levels of S-10013, TNF-α, IL-1β and NF-κB in L group decreased, and those of IL-10 increased. It can be concluded that LXA4 pretreatment can improve the cognitive function in aged rats after global cerebral ischemia reperfusion probably by inhibiting the inflammatory reaction.