FNDC5/Irisin in dementia and cognitive impairment: update and novel perspective

Epidemiological surveys show that the incidence of age-related dementia and cognitive impairment is increasing and it has been a heavy burden for society, families, and healthcare systems, making the preservation of cognitive function in an increasingly aging population a major challenge. Exercise is beneficial for brain health, and FDNC5/irisin, a new exercise-induced myokine, is thought to be a beneficial mediator to cognitive function and plays an important role in the crosstalk between skeletal muscle and brain. This review provides a critical assessment of the recent progress in both fundamental and clinical research of FDNC5/irisin in dementia and cognitive impairment-related disorders. Furthermore, we present a novel perspective on the therapeutic effectiveness of FDNC5/irisin in alleviating these conditions.

Relationship between haptoglobin gene polymorphism and disease severity and susceptibility in senile vascular dementia patients / 国际检验医学杂志

Objective To explore the relationship between haptoglobin gene polymorphism and disease se-verity and susceptibility in senile vascular dementia patients.Methods A total of 80 patients with senile vas-cular dementia admitted to the hospital from February 2018 to February 2023 were selected as the vascular de-mentia group,and 80 stroke patients with non-vascular dementia admitted to the hospital during the same pe-riod were selected as the control group.The genotype distribution and allele frequency of haptoglobin gene were measured using polymerase chain reaction with sequence-specific primers,and their relationship with the severity and susceptibility of vascular dementia patients was analyzed.Results The proportion of history of hyperlipidemia and diabetes mellitus and the levels of total cholesterol and triglyceride in vascular dementia group were higher than those in control group,the differences were statistically significant(P＜0.05).The distribution of genotypes was in Hardy-Weinberg equilibrium(P＞0.05).The frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele in vascular dementia group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in the scores of mini-mental state examination and hachinski ischaemic score among patients with vascular dementia with different haptoglobin genotypes(P＜0.05).Multivariate Logistic regression analysis showed that the carrier of hapto-globin 2-2 genotype and the carrier of haptoglobin 2 allele were independent risk factors for vascular dementia(P＜0.05).Conclusion Haptoglobin 2-2 genotype and haptoglobin 2 allele distribution frequency are associ-ated with the occurrence of vascular dementia after stroke,and those with high frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele distribution suffer a severe disease,which can provide reference for early i-dentification and assessment of vascular dementia.

Effect of catgut implantation at acupoint on the learning and memory function and hippocampal microangiogenesis in vascular dementia rats / 解剖学报

Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.

Safety Evaluation of Tianzhi Granules in Treating Mild-to-moderate Vascular Dementia / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Tianzhi granules used in the treatment of mild-to-moderate vascular dementia. MethodA randomized， double-blind， double-simulated， positive drug/placebo parallel controlled multi-center phase Ⅳ clinical trial and an open multi-center phase Ⅳ clinical trial of Tianzhi granules in the treatment of mild-to-moderate vascular dementia were conducted. Safety data of 1 492 patients were included and analyzed according to inclusion and exclusion criteria. The main evaluation measures were the incidence rate of adverse events/adverse reactions， laboratory indicators， vital signs， and electrocardiogram （ECG） results. ResultA total of six adverse events possibly related to the test drug occurred in 520 patients of the double-blind trial， and the symptoms were all mild and recovered. The incidence of adverse events was not statistically different among Tianzhi granules， donepezil， and placebo groups. Nine adverse events possibly related to the test drug were observed in 972 patients of the open trial， and the symptoms were mild and recovered. Laboratory tests （blood routine， urine routine， liver function， kidney function， and coagulation） and vital signs were compared before treatment （baseline） and after treatment of 12 and 24 weeks， respectively. There was no statistical significance in the main indicators before and after treatment. In the double-blinded trial， there was no significant difference in safety indicators between different groups before and after treatment. The most frequent adverse reaction was gastrointestinal discomfort， with an incidence rate of 6.64‰. ConclusionAdverse reactions occasionally occur in patients using Tianzhi granules， and it is safe to use Tianzhi granules to treat mild-to-moderate vascular dementia clinically.

Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

Effects of different duration of exercise preconditioning on cerebral blood flow and microglia activation related proteins in rats with vascular dementia / 中国康复医学杂志

Objective:To explore the effects of different duration of exercise preconditioning on changes in cerebral blood flow and microglia activation related proteins in rats with vascular dementia. Method:Sixty SPF SD male rats were used to prepare vascular dementia rat models by permanent ligation of bilateral common carotid arteries.They were randomly divided into the model group,sham-operated group,ex-ercise preconditioning 4-week model group,exercise preconditioning 4-week sham-operated group,exercise pre-conditioning 2-week model group and exercise preconditioning 2-week sham-operated group,with 10 rats in each group.The exercise preconditioning 4-week rats received 30 minutes of moderate intensity non-weight-bear-ing swimming training 5 times a week for 4 weeks before modeling,while the exercise preconditioning 2-week rats received the same training for 2 weeks.Morris water maze was used to detect the spatial learning and memory ability of rats,laser speckle imaging technique was used to observe the changes of cerebral blood flow and the opening of collateral circulation of rats at different time point before and after the model-ing,and Western Blotting was used to detect the expression of TLR4 and Iba 1 protein in hippocampus. Result:Compared with the sham-operated group and the exercise preconditioning 2-week sham-operated group,the average escape latency time of rats in the exercise preconditioning 4-week sham-operated group,the model group,the exercise preconditioning 4-week model group and the exercise preconditioning 2-week model group was significantly prolonged(P＜0.05).Compared with the exercise preconditioning 4-week sham-operated group,the average escape latency time of rats in the model group and the exercise preconditioning 4-week model group was significantly prolonged(P＜0.05).Compared with the model group and exercise preconditioning 4-week model group,the average escape latency time of rats in exercise preconditioning 2-week model group was significantly decreased(P＜0.05).The simple effect of repetitive measurement deviation analysis suggested that the average cerebral blood flow before modeling,2h after modeling,3d after modeling and 7d after model-ing was statistically significant between the groups(P＜0.05).The simple effect of time factor on average cere-bral blood flow of the model group,the exercise preconditioning 4-week model group and the exercise precon-ditioning 2-week model group was statistically significant(P＜0.01).The opening of collateral circulation of rats in each group was observed.Compared with the model group,less reduction in microvessel diameter was ob-served in the exercise preconditioning 2-week model group(P＜0.05).Compared with the sham-operated group,the exercise preconditioning 4-week sham-operated group and the exercise preconditioning 2-week sham-operat-ed group,Ibal and TLR4 protein expressions in the model group were significantly increased(P＜0.01).Com-pared with the model group,Ibal and TLR4 protein expressions in the exercise preconditioning 2-week model group were decreased(P＜0.05). Conclusion:Moderate intensity exercise preconditioning for 2 weeks can improve the learning and memory abili-ty of vascular dementia rats,but exercise preconditioning for 4 weeks has no obvious effect on the improve-ment of learning and memory ability.The mechanism may be related to the improvement of cerebral blood flow status and the inhibition of microglia activation.

Tectorigenin improves cognitive deficits in rats with vascular dementia by regulating TLR4/MyD88/NF-κB signaling pathway / 中国免疫学杂志

Objective:To analyze effects of tectorigenin on improving cognitive deficits in rats with vascular dementia(VD)by regulating Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods:A total of 72 rats were randomly divided into sham operation group,model group,low,medium and high doses[25,50,100 mg/(kg·d)]tectorigenin groups and positive control group[piracetam 324 mg/(kg·d)],with 12 rats in each group.Except for sham operation group,VD models were replicated in other groups.After successful modeling,different doses tectorigenin groups and positive control group were administered intragastrically with different doses of tectorigenin and piracetam,while other groups were administered intragastrically with same volume of normal saline for 28 d.Spatial learning and memory ability were detected by Morris water maze.Neurotransmitter levels in hippocampus interstitial fluid were detected by high performance liquid chromatography-electro-chemical.Brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor b(TrkB)expressions in hippocampus were detected by RT-qPCR and Western blot.TLR4/MyD88/NF-κB pathway-related proteins in hippocampus were detected by Western blot.Results:Compared with sham operation group,escape latency was longer,while stay time in target area and times of crossing platform were lower in model group(P<0.05).Compared with model group,escape latency was shorter,while stay time in target area and times of crossing platform were higher in medium and high doses tectorigenin groups(P<0.05).NE,DA,5-HT and 5-HIAA levels in model group were lower than those in sham operation group(P<0.05),which were higher in medium and high doses tectorigenin groups than model group(P<0.05).Compared with sham operation group,BDNF and TrkB mRNA and proteins levels were lower,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were higher in model group(P<0.05).Compared with model group,BDNF and TrkB mRNA and proteins levels were higher,while TLR4,MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were lower in medium and high doses tectorigenin groups(P<0.05).Conclusion:Tectorigenin can improve cognitive deficits in VD rats,which may be related to regulating TLR4/MyD88/NF-κB signaling pathway.

Visualization Analysis on Research Literature about Acupuncture Treatment of Vascular Dementia from 2003 to 2023 / 中国中医药信息杂志

Objective To analyze the status and development direction of acupuncture treatment for vascular dementia from 2003 to 2023;To provide reference for related research.Methods Relevant literature on acupuncture treatment for vascular dementia was retrieved from CNKI,Wanfang Data,and VIP from January 2003 to September 2023.NoteExpress 3.7.0 and CiteSpace 5.7.R5 software were used to analyze keywords,authors,research institutions,and visualize knowledge maps.Results A total of 934 articles were included in the analysis,showing a slow fluctuating upward trend in publication volume.The study involved 653 authors,with prolific contributors such as Lai Xinsheng,Liu Zhibin,and Niu Wenmin.It included 449 research institutions,with prominent contributors being the First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Heilongjiang University of Chinese Medicine,and Guangzhou University of Chinese Medicine.Additionally,635 keywords were identified,forming 23 clusters.High-frequency keywords included"cognitive function","rats",and"hippocampus".Conclusion The protection and repair of nerves by acupuncture,the improvement of cognitive function,the comprehensive treatment mode,and the prevention of vascular dementia may be the research hotspots and trends in this field.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Association, pathological mechanisms, prevention and control strategies of diabetes and vascular dementia: a review / 预防医学

@#The incidence rate of vascular dementia is increasing year by year, and there is still no effective treatment at present, so it is very important to reduce the risk of developing vascular dementia. Research shows that diabetes is associated with vascular dementia. Based on the research literature related to diabetes and vascular dementia from January 1995 to April 2023, This article reviews the relationship between diabetes and vascular dementia, pathological mechanism and prevention and control strategies. It is found that diabetes can promote the occurrence and development of vascular dementia by inducing cerebrovascular disease, oxidative stress and inflammatory reaction, using hypoglycemic drugs, removing the incentives of cerebrovascular disease, maintaining the stability of blood-brain barrier and adhering to a healthy lifestyle are the main measures for the prevention and control of vascular dementia at this stage. Future research needs to further explore the mechanism of vascular dementia induced by diabetes, and seek economic and effective prevention targets.

Pathogenesis and Treatment of Vascular Dementia Based on Integrated Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Vascular dementia （VaD） is a common disease that affects the health of the elderly. Due to the aging of the social population， the incidence of VaD is increasing year by year. There have been no officially approved treatments for this disease， mainly because its pathogenesis is complex， and the mechanism of action of effective drugs is not yet clear， which hinders drug research for the treatment of VaD. Therefore， by reviewing the available literature related to VaD， this study sorted out the pathogenesis of VaD from traditional Chinese medicine （TCM） and western medicine， and concluded that in TCM， VaD was characterized by the deficiency of the spleen and kidney （deficiency） and combination of phlegm and blood stasis （excess）， while in western medicine， the pathogenesis of VaD is mainly inflammatory response， oxidative stress， abnormal expression of related proteins， and dysfunction of signaling pathways. On this basis， this study also summarized the research on the mechanism of action of commonly used single Chinese herbal medicine and Chinese herbal medicine compound， western medicine， and the combination of Chinese herbal medicine and western medicine in the treatment of VaD in recent years. The commonly used single Chinese herbal medicine Ginkgo Folium and Chinese herbal medicine compound Dihuang Yinzi have the multi-component and multi-target characteristics and few adverse reactions in the treatment of VaD， while the commonly used western medicines such as donepezil and memantine have the characteristics of the clear target and quick onset. The combination of Chinese herbal medicine and western medicines can achieve a better effect. This study summarized the research on the pathogenesis and treatment of VaD， aiming to link the pathogenesis of VaD with the mechanism of effective drug therapy， and provide an important reference for future drug development for the treatment of VaD.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer's disease and vascular dementia / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.

Research Overview and Development Trend Analysis of Acupuncture Treatment of Vascular Dementia Based on Bibliometrics / 世界科学技术-中医药现代化

Objective To summarize the progress of domestic researches on acupuncture treatment for vascular dementia(VaD)with visual analysis method.Methods The literatures related to acupuncture for VaD in Chinese National Knowledge Infrastructure(CNKI)were searched,and the co-occurrence mapping of authors,research institutions and keywords of related literatures were generated and analyzed using CiteSpace software.Results A total of 1296 relevant literatures were retrieved,1289 of which met the inclusion criteria,and the annual number of articles were increasing in recent years.A total of 778 authors were included,72 of whom published more than 5 articles,three major cooperation teams were formed which led by Lai Xinsheng,Cheng Hongliang and Liu Cunzhi.350 institutions were included,among which 23 institutions published more than 10 papers.The main research institutions included Guangzhou University of Chinese Medicine,Anhui University of Chinese Medicine,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,etc.A total of 510 keywords were included,among which 41 keywords appeared more than 10 times.Seven natural clusters were formed mainly including"dementia""cognitive impairment""electroacupuncture""SanYinJiao""acupuncture""acupuncture and moxibustion""total effective rate""calcium channel blocker".Conclusion Research on acupuncture treatment of VaD has always been an important position in the field of traditional Chinese medicine research.However,the research lacks systematization and needs to strengthen multidisciplinary cross-collaboration among multiple institutions.Acupuncture of VaD focuses on animal experiments and small clinical studies.In the future,multicenter,large-sample,high-quality clinical studies should be developed,and mechanisms should be investigated based on the determination of efficacy.

Acupuncture Improve Scognitive Function of Vascular Dementia Rats by Regulating TLR-4/MyD88/NF-κB Pathway / 世界科学技术-中医药现代化

Objective To study the effect of acupuncture on the effect of acupuncture on the learning and memory ability and inflammatory factor expression in rats with vascular dementia,to provides an experimental basis for acupuncture and treatment of vascular dementia.Methods Randomly dividing thirty-six SPF grade SD male rats into 12 rats in sham surgery(A),model(B),and acupuncture(C).Groups B and C will prepare the VD model,and Group A will only surgically isolated the bilateral common carotid arteries without ligation.In Group C,acupuncture with"Baihui","Shenshu"and"Fenglong"points were used for intervention,each course lasts for 6 days,for a total of 2 sessions;Group A and Group B were fed normally without intervention.Morris water maze experiment was used to assess spatial learning and memory,ELISA for serum IL-1β and TNF-α,Real-time PCR for TLR-4,MyD88 and NF-κB mRNA,positive expression of Iba1 and NF-κB,and Western blot for relative expression levels of IL-1β and TNF-α in hippocampus.Results Compared with group B,group C rats had a shorter escape latency period(P<0.01)and had crossed the platform more often(P<0.05);The serum concentrations of TNF-α and IL-1β were significantly decreased(P<0.01);The expression amount of mRNA of TLR-4/MyD88/NF-κB was significantly reduced in the hippocampus(P<0.01);The positive expression of Iba1 and NF-κB protein in the brain was significantly reduced(P<0.01);The relative expression level of TNF-α and IL-1β in the hippocampus was significantly reduced(P<0.01).Conclusion Needle"Baihui","Shenshu"and"Fenglong"can improve vascular dementia rats cognitive dysfunction,and the mechanism may be related to the inhibition of neuroinflammatory response by inhibiting TLR-4/MyD88/NF-κB signaling pathway activity.

Research progress on the mechanism of cerebral white matter lesions in vascular dementia caused by chronic cerebral hypoperfusion / 中风与神经疾病杂志

@#Chronic cerebral hypoperfusion (CCH) is a potential important pathological factor leading to cognitive impairment in vascular dementia (VaD). The pathological mechanisms are complex and diverse,with cerebral white matter lesions being the main pathological feature,which is present throughout the entire progression of cognitive impairment caused by CCH. Dysfunction of the blood-brain barrier and neuroinflammatory responses caused by chronic cerebral hypoperfusion are important causes of cerebral white matter lesions. This article discusses the relationship between cerebral white matter lesions and VaD and the improvement of cerebral white matter lesions in VaD to slow down its development and progression,and explores the mechanism and therapeutic methods for VaD,aiming to find therapeutic targets of VaD to prevent its occurrence and improve symptoms.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

Puerarin reduces intracellular Ca2+ concentration and upregulates BDNF to protect hippocampal neurons in vascular dementia rats / 西安交通大学学报(医学版)

【Objective】 To observe the effect of puerarin on the concentration of Ca2+ and the expression of brain derived neurotrophic factor (BDNF) in hippocampal neurons of vascular dementia (VD) rats so as to explore the mechanism of puerarin in protecting nerve cells. 【Methods】 Male SD rats were randomly divided into sham operation group, model group, and puerarin intervention group. The vascular dementia model was established by ligating bilateral common carotid arteries at intervals of 3 days. Two weeks after the operation, the learning and memory abilities of the rats were evaluated by Morris water maze, and the expression of BDNF in the hippocampus of the rats was detected by immunohistochemistry and Western blotting. The mean fluorescence intensity was measured by flow cytometry to represent the intracellular free Ca2+ concentration. 【Results】 In the puerarin intervention group, the rats’ escape latency in Morris water maze was significantly shortened, the expression of BDNF in the hippocampus was significantly increased, and the concentration of Ca2+ in hippocampal neurons was decreased. Compared with the model group, the difference was statistically significant (all P<0.05). 【Conclusion】 Puerarin has neuroprotective effect on VD rats, and its mechanism may be related to the decrease of Ca2+ concentration in hippocampal neurons and the up-regulation of BDNF expression.

Mechanism of electroacupuncture regulating the ligand pathway of tyrosine kinase receptor in improving vascular dementia / 解剖学报

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism / 解剖学报

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A ( PKA) , cyclic adenosine monophosphate response element binding protein( CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats. Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n= 13) , vascular dementia group (VD, n= 13) and vascular dementia treaded with exercise group (VD + EX, n= 13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Moms water maze test ( MWM ) , glutamic ( Glu ) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography( HPLC) ; the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting. Results The result of the MWM showed the average escape latency of rats in the VD group on the 1 -5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly ( P 0. 05 ) between the two groups. Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.