Clinical Report on the Treatment of Post-stroke Cognitive Impairment Based on Microbe-Gut-Brain Axis Theory

Based on the close relationship between MGBA and PSCI,one PSCI related case is reported,and it is emphasized to improve clinicians'understanding of MGBA theory in the treatment of PSCI,thereby providing new ideas for exploring pathogenesis and treatment of PSCI.

C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization

BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

Enhancing Mild Cognitive Impairment Detection through Efficient Magnetic Resonance Image Analysis

Neuroimaging has emerged over the last few decades as a crucial tool in diagnosing Alzheimer’s disease(AD).Mild cognitive impairment(MCI)is a condition that falls between the spectrum of normal cognitive function and AD.However,previous studies have mainly used handcrafted features to classify MCI,AD,and normal control(NC)individuals.This paper focuses on using gray matter(GM)scans obtained through magnetic resonance imaging(MRI)for the diagnosis of individuals with MCI,AD,and NC.To improve classification performance,we developed two transfer learning strategies with data augmentation(i.e.,shear range,rotation,zoom range,channel shift).The first approach is a deep Siamese network(DSN),and the second approach involves using a cross-domain strategy with customized VGG-16.We performed experiments on the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset to evaluate the performance of our proposed models.Our experimental results demonstrate superior performance in classifying the three binary classification tasks:NC vs.AD,NC vs.MCI,and MCI vs.AD.Specifically,we achieved a classification accuracy of 97.68%,94.25%,and 92.18%for the three cases,respectively.Our study proposes two transfer learning strategies with data augmentation to accurately diagnose MCI,AD,and normal control individuals using GM scans.Our findings provide promising results for future research and clinical applications in the early detection and diagnosis of AD.

Trends in the Application of Dyadic Coping in Older Adults with Mild Cognitive Impairment and Their Spouses

Dyadic coping plays an important role in older adults with mild cognitive impairment and their spouses. Significant correlations were found between dyadic coping and self-efficacy, anxiety and depression, marital quality, and quality of life in elderly patients with mild cognitive impairment and their spouses, and there were gender differences, with a 36.1% [P = 0.028, OR = 0.639, 95% CI (0.429, 0.952)] and 54% [P = 0.004, OR = 0.460, 95% CI (0.269, 0.785)] reduction in the risk of MCI and dementia for older men aged 65 - 69 years with a spouse and for those aged 80 years and older with a spouse, respectively. In contrast, there was no significant difference in the association between having or not having a spouse and developing MCI and dementia in older women (all P > 0.05). Psychosocial interventions, skills interventions, and exercise from the perspective of dyadic relationships were effective in improving the physical and mental health of older adults with mild cognitive impairment and their spouses. However, there is a lack of specific intervention programs for dyadic relationships in the local cultural context as an entry point. Therefore, it is necessary to draw on internal and external relevant literature to treat both partners as a whole for intervention, provide personalized social, cognitive and motor therapy for patients and promote the integration and participation of caregivers, help patients and spouses to improve the sense of well-being and intimacy, reduce the burden of caregivers, and build a dyadic coping intervention program suitable for elderly patients with mild cognitive impairment in China. The current article aims to provide a conceptual review focusing on dyadic coping care to inform the development of a dyadic intervention program suitable for older adults with mild cognitive impairment in China. This review outlines the theoretical concepts, assessment tools, current state of research, and intervention methods for mild cognitive impairment and dyadic coping.

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Risk factors for cognitive impairment in patients with chronic kidney disease

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s lymphoma.Whether patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully investigated.therapy have cognitive impairment has not been fully investigated.AIM To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.METHODS The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after chemo-therapy.RESULTS The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT groups.CONCLUSION Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

Clinical efficacy of Baijin pills in the treatment of generalized tonicclonic seizure epilepsy with cognitive impairment

BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

Exploring the therapeutic potential of Qi Teng Mai Ning recipe in ischemic stroke and vascular cognitive impairment

Background:This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy,with a focus on identifying its active ingredients and their target proteins.Methods:The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe.It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database.These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe’s core active ingredients.In vitro cell experiments were conducted on hypoxic HT22 cells,involving CCK8 assay,lentiviral transfection to silence autophagy related 9B(ATG9B),immunofluorescence staining,and qPCR validation to investigate the effects of the recipe on autophagy.Results:The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network.Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs.Molecular docking showed quercetin,kaempferol,myrcene,and conferone as key ingredients targeting autophagy-related proteins.Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions,reduced apoptosis,and modulated the expression of autophagy-related factors,thereby decreasing apoptosis rates in HT22 cells.Conclusion:The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins.Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions,though further research is needed to fully understand its mechanisms and clinical applications.

Cognitive impairment in patients with bipolar disorder alone versus those with bipolar disorder comorbid with borderline personality disorder

BACKGROUND Bipolar disorder(BD)is a severe mental illness.BD often coexists with borderline personality disorders,making the condition more complex.AIM To explore the differences in cognitive impairment between patients with BD and those with BD comorbid with borderline personality disorder.METHODS Eighty patients with BD and comorbid borderline personality disorder and 80 patients with BD alone were included in groups A and B,respectively,and 80 healthy volunteers were included as controls.Cognitive function in each group was evaluated using the Chinese version of the repeatable battery for the assess-ment of neuropsychological status(RBANS),the Stroop color-word test,and the Wechsler intelligence scale-revised(WAIS-RC).RESULTS The indices of the RBANS,Stroop color-word test,and WAIS-RC in groups A and B were significantly lower than those of the control group(P<0.05).Group A had significantly longer Stroop color-word test times for single-character,single-color,double-character,and double-color,lower scores of immediate memory,visual breadth,verbal function dimensions and total score of the RBANS,as well as lower scores of verbal IQ,performance IQ,and overall IQ of the WAIS-RC compared with group B(P<0.05).Compared to group B,group A exhibited significantly longer single-character time,single-color time,double-character time,and double-color time in the Stroop color-word test(P<0.05).CONCLUSION The cognitive function of patients with BD complicated with borderline personality disorder is lower than that of patients with BD.

Estimating High-Order Functional Connectivity Networks for Mild Cognitive Impairment Identification Based on Topological Structure

Functional connectivity networks (FCNs) are important in the diagnosis of neurological diseases and the understanding of brain tissue patterns. Recently, many methods, such as Pearson’s correlation (PC), Sparse representation (SR), and Sparse low-rank representation have been proposed to estimate FCNs. Despite their popularity, they only capture the low-order connections of the brain regions, failing to encode more complex relationships (i.e. , high-order relationships). Although researchers have proposed high-order methods, like PC + PC and SR + SR, aiming to build FCNs that can reflect more real state of the brain. However, such methods only consider the relationships between brain regions during the FCN construction process, neglecting the potential shared topological structure information between FCNs of different subjects. In addition, the low-order relationships are always neglected during the construction of high-order FCNs. To address these issues, in this paper we proposed a novel method, namely Ho-FCNTops, towards estimating high-order FCNs based on brain topological structure. Specifically, inspired by the Group-constrained sparse representation (GSR), we first introduced a prior assumption that all subjects share the same topological structure in the construction of the low-order FCNs. Subsequently, we employed the Correlation-reserved embedding (COPE) to eliminate noise and redundancy from the low-order FCNs. Meanwhile, we retained the original low-order relationships during the embedding process to obtain new node representations. Finally, we utilized the SR method on the obtained new node representations to construct the Ho-FCNTops required for disease identification. To validate the effectiveness of the proposed method, experiments were conducted on 137 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to identify Mild Cognitive Impairment (MCI) patients from the normal controls. The experimental results demonstrate superior performance compared to baseline methods.

Clinical observation of taking acupuncture at the acupoints based on "four seas theory" for post-stroke cognitive impairment

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.

P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice

Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.

Clinical study on Jin's three-needle therapy for post-stroke cognitive impairment

Objective:To observe the clinical efficacy of Jin's three-needle therapy on post-stroke cognitive impairment(PSCI)and the effect on neuroelectrophysiology(event-related potentials).Methods:A total of 60 PSCI patients were selected and divided into a treatment group and a control group according to the method of random number table,with 30 cases in each group.The patients in the control group received routine treatment while the patients in the treatment group received additional Jin's three-needle therapy.The treatment for both groups lasted four weeks.Mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores as well as amplitude and latency of potential 300(P300)were adopted to compare the between-group results before and after treatment.Results:Before treatment,there were no significant differences(all P>0.05)in MMSE and MoCA scores,P300 latency and P300 amplitude between the two groups.After 4 weeks of treatment,the MMSE and MoCA scores and P300 amplitudes were improved in both groups,and the P300 latencies became shorter.The results showed significant intra-group and between-group differences(all P<0.05).Conclusion:Based on the routine treatment,Jin's three-needle therapy is effective for PSCI.The mechanism is probably through its regulation on the patients'neuroelectrophysiology.

β2-Microglobulin exacerbates neuroinflammation,brain damage,and cognitive impairment after stroke in rats

β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.