[Mechanism of electroacupuncture for vascular dementia based on proteomics].

OBJECTIVE: To explore the potential mechanism of electroacupuncture (EA) for vascular dementia (VD) using tandem mass tag (TMT) quantitative proteomics technology. METHODS: Among 80 male SPF SD rats, 78 rats which met the selection criteria through the Morris water maze test were selected and randomly divided into a sham surgery group (18 rats) and a surgery group (60 rats). VD model was established by four-vessel occlusion (4-VO) method in the surgery group, and 36 rats with successful modeling were randomly assigned to a model group (18 rats) and an EA group (18 rats). Each group was further divided into three subgroups based on intervention duration, with each subgroup containing 6 rats. Seven days after model establishment, the EA group received EA intervention at left and right "Sishencong" (EX-HN 1) and bilateral "Fengchi" (GB 20), with continuous wave at a frequency of 2 Hz and current intensity of 1 mA, daily for 30 min, with subgroups receiving EA for 7, 14, or 21 d respectively. Cognitive function before and after interventions was assessed using Morris water maze. Proteomic analysis was conducted on the optimal EA subgroup and corresponding sham surgery and model subgroups, identifying differentially expressed proteins and analyzing them through bioinformatics. Differentially expressed target proteins was performed using parallel reaction monitoring (PRM) and Western blot techniques. RESULTS: Compared to the sham surgery group, the model group exhibited prolonged escape latency and reduced number of platform crossings (P<0.01); compared with model group, the EA group showed reductions in escape latency and increased platform crossings after 7, 14, and 21 days of intervention (P<0.01, P<0.05). Compared to the 7 and 14-day intervention, the rats in the EA group of 21-day intervention showed the most significant improvements in reductions of escape latency and increased platform crossings (P<0.01, P<0.05), and was selected for further proteomic, PRM analyses, and Western blot validation. Compared to the sham surgery group, the model group displayed 71 differentially expressed proteins, with 50 up-regulated and 21 down-regulated proteins; compared to the model group, the EA group had 54 differentially expressed proteins, with 30 up-regulated and 24 down-regulated proteins. Functional enrichment and clustering analyses indicated that these proteins were primarily associated with cellular processes, metabolic processes, phagocytosis recognition, immune response, and regulation of extracellular matrix, etc. Enrichment was observed in the mammalian target of rapamycin (mTOR) signaling pathway and neurotrophic factors signaling pathways, involving glycogen synthase kinase 3ß (GSK3ß) and mitogen-activated protein kinase kinase 2 (Map2k2), with PRM and Western blot findings consistent with the proteomic results. Which meant that compared with the model group, the protein expression of GSK3ß and Map2k2 of hippocampus was increased in the EA group (P<0.01, P<0.05). CONCLUSION: EA at "Sishencong" (EX-HN 1) and "Fengchi" (GB 20) could improve cognitive function in VD rats, with the mechanism involving multiple targets and pathways, potentially related to GSK3ß, Map2k2 proteins, and the mTOR and neurotrophic factor signaling pathways.

Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia.

AIM: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. BACKGROUND: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. OBJECTIVE: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. METHODS: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. RESULTS: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. CONCLUSION: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.

Acupoint catgut embedding improves learning and memory impairment in vascular dementia rats.

Background: Vascular dementia (VD) is a disease that affects brain function through cerebrovascular disease. Due to its complex pathogenesis, there is no effective drug treatment for VD. The present study aimed to evaluate the role of acupoint catgut embedding in the treatment of rats with VD and its possible molecular mechanism. Methods: A modified 4 vessel occlusion (4-VO) method was used to establish a VD model rat, and spatial learning and memory ability was assessed using the Morris water maze (MWM) test. The protein expression levels were detected by Western blot. Hematoxylin and eosin (HE) staining was used for histological analysis and enzyme-linked immunosorbent assay (ELISA) was applied for analysis of serum inflammatory factors. Results: We successfully constructed VD model rats with spatial learning and memory impairment, hippocampus injury, and high inflammatory response. Treatment of VD rats with acupoint catgut embedding significantly reduced escape latency and increased the time in the target quadrant and platform crossing times. VD-mediated hippocampal tissue damage and inflammatory reaction [down-regulating interleukin-1ß (IL-1ß), interleukin-6 (IL-6)] were significantly alleviated by acupoint catgut embedding treatment. In addition, further mechanism exploration found that acupoint catgut embedding treatment could improve the activity of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. In summary, acupoint catgut embedding treatment improved spatial learning and memory loss, alleviated pathological damage of the hippocampus, and inhibited inflammation response in VD rats, which was probably related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway. Conclusions: Acupoint catgut embedding may warrant further study as an adjuvant therapy for the treatment of VD.

Effect of Modified Shuyuwan on Hippocampal Myelin Sheath Injury in Vascular Dementia Rats Through Cx43/Glu/AMPAR Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of modified Shuyuwan （SYW） on hippocampal myelin sheath injury in vascular dementia （VD） model rats. MethodSixty male SD rats of SPF grade were randomly divided into sham operation group， model group， and high-， medium- and low-dose modified SYW groups， with 12 rats in each group. The VD model was induced by bilateral carotid artery ligation in rats of the groups except for those of the sham operation group. After modeling， rats were screened by the water maze test， followed by drug treatment by gavage. Specifically， rats in the modified SYW groups were treated with modified SYW at 10， 5， 2.5 g·kg-1·d-1， accordingly， and those in other groups were administered with the same amount of normal saline. After intragastric administration for 28 days， the spatial learning and memory abilities of rats were detected by the water maze test. The hippocampal neuron structure was observed by hematoxylin-eosin （HE） staining. The content of hippocampal tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， and glutamate （Glu） was observed by biochemical detection. The hippocampal expression of myelin basic protein （MBP）， astrocyte activation marker glial fibrillary acidic protein （GFAP）， and connexin 43 （Cx43） was detected by immunofluorescence detection. The myelin sheath structure in the hippocampus was observed by the electron microscope. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor （AMPAR） and Cx43 protein expression was detected by Western blot. ResultCompared with the sham operation group， the model group showed prolonged escape latency （P<0.01）， decreased times of crossing the original platform and percentage of target quadrant detention time （P<0.01）， disordered neuron structure in the hippocampal CA1 region， loose myelin sheath lamella with blurry edge， up-regulated expression levels of TNF-α， IL-6， and Glu in the hippocampal CA1 region， especially Glu （P<0.01）， reduced expression of AMPAR （P<0.01）， increased protein expression of p-AMPAR and Cx43 （P<0.01）， significantly dwindled protein expression of MBP in the myelin sheath， and enhanced fluorescence co-labeled by GFAP and Cx43. Compared with the model group， the modified SYW groups showed shortened escape latency （P<0.05）， increased times of crossing the original platform and percentage of target quadrant detention time （P<0.05）， closely arranged hippocampal neuron structure， denser myelin sheath lamella with clear edge， down-regulated expression levels of TNF-α， IL-6， and Glu in the hippocampal CA1 region， especially Glu （P<0.01）， up-regulated AMPAR （P<0.01）， reduced protein expression of p-AMPAR and Cx43， especially in the high-dose group （P<0.01）， significantly elevated protein expression of MBP in the myelin sheath， and weakened fluorescence co-labeled by GFAP and Cx43， especially in the high-dose group. ConclusionModified SYW can improve the learning and memory abilities of VD rats， and the mechanism may be related to the inhibition of Cx43 expression， reduction of the release of Glu， inhibition of AMPAR-mediated inflammatory response to reduce the production of astrocyte marker GFAP， and promotion of the expression of MBP protein to alleviate myelin injury.

Comparative Efficacy and Acceptability of Cholinesterase Inhibitors and Memantine Based on Dosage in Patients with Vascular Cognitive Impairment: A Network Meta-analysis.

BACKGROUND: Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted. RESULTS: Eleven RCTs were included. Compared with the placebo, in terms of efficacy, donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective for the cognition of ADAS-cog, and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits for the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements for CDR-SB and EXIT25, respectively. In terms of acceptability, memantine was found to be the best. CONCLUSION: Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg exerted beneficial effects on cognition, and donepezil 10mg provided beneficial effects for executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but doserelated adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice in terms of efficacy and safety.

[Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia].

OBJECTIVE: To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD. METHODS: Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus. RESULTS: Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (P<0.01). After intervention, the escape latency in the moxibustion group and the medication group was shorter than that before intervention (P<0.01). Compared with the model group, the escape latency in the moxibustion group and the medication group was shortened (P<0.05); compared with the medication group, the escape latency in the moxibustion group was shortened (P<0.05). Compared with the normal group and the sham operation group, the apoptosis rate of neurons in hippocampal CA1 area was increased, the number of Bcl-2/NeuN co-expression positive cells was decreased, and the number of Bax/NeuN co-expression positive cells was increased in the model group (P<0.01); compared with the model group, the apoptosis rates of hippocampal CA1 neurons were decreased, the number of Bcl-2/NeuN co-expression positive cells was increased, and the number of Bax/NeuN co-expression positive cells was decreased in the moxibustion group and the medication group (P<0.01); compared with the medication group, the apoptosis rate of neurons in hippocampal CA1 area was decreased, the number of Bcl-2/NeuN co-expression positive cells was increased, and the number of Bax/NeuN co-expression positive cells was decreased in the moxibustion group (P<0.01, P<0.05). Compared with the normal group and the sham operation group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the model group were increased (P<0.01); compared with the model group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the moxibustion group and the medication group were decreased (P<0.01); compared with the medication group, the expressions of cytC, Tom20 protein in hippocampal CA1 area and PUMA protein in hippocampal tissue in the moxibustion group were decreased (P<0.05, P<0.01). CONCLUSION: Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD.@*METHODS@#Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus.@*RESULTS@#Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (@*CONCLUSION@#Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Effect of Allicin on Learning and Memory Ability of Vascular Dementia Rats and Its Mechanism / 中国实验方剂学杂志

Objective:To investigate the effect of allicin （ALL） on learning and memory ability of rats with vascular dementia （VD） and the possible mechanism. Method:The VD rats induced by modified bilateral common carotid artery occlusion （BCCAO） were randomly divided into the VD group， low- and high-dose ALL （ALL-L and ALL-H） groups， and the sham operation （S） group， with 15 rats in each group. In the ALL-L and ALL-H groups， ALL was injected into the femoral vein at 5 mg·kg^-1 and 20 mg·kg^-1， respectively， while the same volume of normal saline was injected in the S and VD groups， once a day， for two successive weeks. Morris water maze （MWM） was used to test the learning and memory ability of rats. Hematoxylin and eosin （HE） staining was conducted to observe the pathological changes in hippocampal tissue， followed by the detection of inflammatory factors tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， and IL-1<italic>β</italic> as well as oxidative stress indexes malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in rat hippocampus. The apoptosis of hippocampal cells was detected by TdT-mediated dUTP Nick end Labeling（TUNEL） assay. The expression levels of apoptosis and autophagy-related proteins cysteinyl aspartate-specific protease-3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， LC3Ⅰ， and the mammalian homolog of yeast ATG6 （Beclin 1） in hippocampus were determined by Western blot. Result:The comparison with the VD group revealed that the learning and memory abilities of rats in the ALL-H and ALL-L groups were significantly improved （<italic>P</italic><0.05）. The TNF-<italic>α</italic>， IL-6， IL-1<italic>β</italic>， and MDA levels in hippocampus were lowered （<italic>P</italic><0.05）， whereas the SOD and GSH-Px activities were enhanced （<italic>P</italic><0.05）. The apoptosis rates were declined （<italic>P</italic><0.05）， with an even lower rate noticed in the ALL-H group （<italic>P</italic><0.05）. The expression levels of Caspase-3， Bax， LC3Ⅱ/LC3Ⅰ ratio， and Beclin-1 in the ALL-H and ALL-L groups were significantly down-regulated in contrast to those in the VD group （<italic>P</italic><0.05）， while that of Bcl-2 was up-regulated （<italic>P</italic><0.05）. The ALL-H group exhibited better performances than the ALL-L group （<italic>P</italic><0.05）. Conclusion:ALL could improve the learning and memory ability of VD rats to some extent， which may be attributed to its inhibition against inflammatory reaction， oxidative stress， and neuronal apoptosis and autophagy.

Effect of Bushen Tongluo Prescription on Synaptic Plasticity of Hippocampal Neurons of Vascular Dementia Model Rats Based on PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism. Method:SD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg^-1） group， high-dose （3 g·kg^-1）， medium-dose （1.5 g·kg^-1）， and low-dose （0.75 g·kg^-1） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot. Result:Compared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （<italic>P</italic><0.05）， increased apoptotic cells （<italic>P</italic><0.05）， declining synaptic dendritic spines （<italic>P</italic><0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （<italic>P</italic><0.05），declining apoptotic cells （<italic>P</italic><0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （<italic>P</italic><0.05）. Conclusion:BSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.

[Effect of acupuncture technique of Tiaoxin Tongdu on learning-memory ability and expressions of hippocampal VEGF and Ang-1 in rats with vascular dementia].

OBJECTIVE: To observe the effect of acupuncture technique of Tiaoxin Tongdu on learning-memory ability and expressions of hippocampal vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) in rats with vascular dementia (VD), and to explore the mechanism of acupuncture technique of Tiaoxin Tongdu for VD. METHODS: A total of 24 male SD rats were randomly divided into a sham operation group, a model group, a medication group and an acupuncture group after Morris water maze test, 6 rats in each group. VD model was established by permanent ligation of bilateral common carotid arteries in the model group, the medication group and the acupuncture group. Treatment was given on the next day after successful modeling. The rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20), "Shenting" (GV 24), "Shuigou" (GV 26), "Dazhui" (GV 14), "Fengfu" (GV 16), "Mingmen" (GV 4), "Neiguan" (PC 6), "Daling" (PC 7) and "Laogong" (PC 8) for 30 min; the rats in the medication group were treated with nimodipine solution (0.0625 g/kg) by gavage, once a day, for 2 weeks. Morris water maze test was used to detect the behavior of rats before modeling, 2 weeks after modeling and after intervention; after intervention, the expressions of VEGF and Ang-1 protein in hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the average escape latency of rats in the model group was prolonged (P<0.01), and the times of crossing the original platform were reduced (P<0.01). Compared with the model group, the average escape latency of rats in the medication group and acupuncture group was significantly shortened (P<0.01), and the times of crossing the original platform were increased (P<0.01, P<0.05). Compared with the sham operation group, the expressions of VEGF and Ang-1 protein in hippocampus in the model group were increased (P<0.05, P<0.01). Compared with the model group, the expressions of VEGF and Ang-1 protein in the hippocampus in the medication group and acupuncture group were significantly increased (P<0.01, P<0.05). CONCLUSION: The acupuncture technique of Tiaoxin Tongdu can significantly improve the learning and memory ability of VD rats, and its mechanism may be related to up-regulating the expressions of VEGF and Ang-1 protein in hippocampus and inducing angiogenesis.

Susceptibility Weighted Imaging (SWI) Recommended as a Regular Magnetic Resonance Diagnosis for Vascular Dementia to Identify Independent Idiopathic Normal Pressure Hydrocephalus Before Ventriculo-Peritoneal (V-P) Shunt Treatment: A Case Study.

Idiopathic normal pressure hydrocephalus (INPH) with comorbid vascular dementia (VD) often have poor response to ventriculo-peritoneal (V-P) shunt. Here, three patients over the age of 60 came to the hospital with the similar clinical symptoms, Evan index over 0.3, mini-mental state examination (MMSE) score <27, and cerebrospinal fluid (CSF) pressure under 200 mmH2O. They accepted conventional brain imaging scanning, followed by magnetic resonance-susceptibility weighted imaging (MR-SWI) scanning. We found that MR-SWI could distinguish INPH from leukoaraiosis (LA) and cerebral amyloid angiopathy (CAA), through cerebral microbleed (CMB) images, sharply. We highly recommended incorporation of MR-SWI into INPH international guidance as a routine pre-operative diagnostic method preceding V-P shunt treatment.

Efficacy of electrical acupuncture on vascular cognitive impairment with no dementia: study protocol for a randomized controlled trial.

BACKGROUND: Vascular cognitive impairment with no dementia (VCIND), manifested mainly as mild impairment of concentration and executive function, is the early phase of vascular dementia (VD). Currently, there is no specific treatment for VCIND. We hypothesize that electrical acupuncture can improve the mental and motor functions of patients with VCIND. Thus, we designed this randomized controlled trial to test this hypothesis by comparing the therapeutic effect of electrical acupuncture versus sham acupuncture in patients with VCIND. METHOD/DESIGN: In this single-center 3-year study, 120 eligible patients will be recruited and randomly assigned to receive electrical acupuncture treatment (n = 60) or sham acupuncture (n = 60) for 8 consecutive weeks (24 sessions in total), with the same acupoint prescription (DU20, EX-HN3, DU24, DU17, DU26, EX-HN1, HT7, PC6, GB20, SP6). The primary assessment is the Montreal Cognitive Assessment. The secondary assessments are the Modified Barthel Index and Event-Related Potential. All outcomes will be assessed at baseline, endpoint, and follow-up at 8 and 24 weeks after the end of treatment. DISCUSSION: If the outcome confirms the effectiveness and safety of electrical acupuncture in treating VCIND, this treatment is expected to be promoted in clinical practice to treat such patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-IIR-17011513 ; Registered on 27 May 2017.

Study on epidemiology of cognitive dysfunction after stroke in the population over the age of 45 in Inner Mongolia.

OBJECTIVE: To analyze the prevalence of different degrees vascular cognitive impairment (VCI) in stroke and the characteristics of demography distribution in Inner Mongolia. In order to provide reference data and theoretical guidance for the prevention and treatment of VCI after stroke in the area. METHODS: Stratified multi-stage random sampling was used to extract six regions of Inner Mongolia as the first sampling cluster; and then the corresponding banners (counties) were selected randomly as the secondary sampling cluster; according to the number of patient required to investigation, the corresponding number of communities was randomly selected from the secondary sampling cluster. According to the diagnostic criteria of 'Guidelines for the diagnosis and treatment of vascular cognitive impairment' and National Institute of Neurological Disorders and Stroke convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), we screened all stroke patients aged 45 or older from each community, a total of 444 patients participated in the questionnaire and various scale assessments. RESULTS: The prevalence of VCI, vascular cognitive impairment no dementia and vascular dementia was 80.41%, 34.46% and 45.95% respectively. The prevalence of VCI in stroke was significantly different in different nationality, age and education level (P < 0.05), and there was no significant difference in gender, occupation, marital status and family structure (P > 0.05). CONCLUSION: The prevalence of VCI after stroke was higher in Inner Mongolia, and VCI had a relatively high morbidity in old age people and person with less education in Chinese Han population.

Effects of Naoluo Xintong Decoction on vascular dementia rats' memory and learning, and hippocampal neuronal intracellular calcium concentration / 中成药

AIM To study the effects of Naoluo Xintong Decoction (NLXTD) on vascular dementia (VD)rats' memory and learning,and hippocampal neuronal intracellular calcium concentration.METHODS Rats were divided randomly into model group,NLXTD group (8.54 g/kg),Huperzia-A group (0.06 mg/kg) and sham group.They were made into vascular dementia rats by the improved bilateral carotid artery ligation method (2-VO)thereafter if necessary.After one-month corresponding intragastric administration,the rats were ethologically evaluated by the Morris water maze experiment;their fluorescence intensity of hippocampal neuronal intracellular calcium concentration was determined by flow cytometry,and the expression levels of calcitonin gene related peptide (CGRP) and its hippocampus receptor were detected by enzyme-linked immunosorbent assay (ELISA).RESULTS Compared with the model group,rats in NLXTD group displayed overall superiority to those of the model group in terms of significantly shortened time of escape latency (P ＜0.01),significantly increased number through the platform and the times in the fourth quadrant (P ＜ 0.01),a lower fluorescence intensity indicating a lower hippocampal neuronal intracellular calcium concentration (P ＜ 0.05).CONCLUSION The significant improvement of memory and learning observed among VD rats' due to NLXTD intervention may be attributable to its efficacy in reducing the hippocampal neuronal intracellular calcium concentration by enhancing the expression levels of CGRP and its receptor.

Xiao-Xu-Ming decoction protects against chronic cerebral ischemia injury in rats and profile of differentially expression proteins analysis in hippocampus / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia (VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia. 2-Vessels occlusion (2-VO) has been widely used as a model of VD. Xiao-Xu-Ming decoction, a well-known traditional Chinese medicine prescrip-tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats. METHODS After XXM treatment, rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody. Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics. RESULTS XXM significantly alleviated 2-VO-induced learning and memory deficits, motor ability dysfunction, and neuronal plasticity injury in rats. The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process, etc. The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system. CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.

Cystatin C in Cerebrovascular Disorders.

Cystatin C (CysC), a cysteine protease inhibitor, has been widely proven to be a highly sensitive biomarker to predict the kidney function. The similarity of the renal and cerebral small vessels has awakened a surge of studies suggesting that CysC plays a key role in various cerebrovascular disorders. This review focuses on four major mechanisms of CysC in a variety of cerebrovascular diseases. (1) The property of the CysC Leu-68-Gln (L68Q) variant to aggregate and the property of the wild type CysC protein to co-aggregate with Amyloid-ß (Aß); (2) The disruption of equilibrium between CysC and related cysteine proteases; (3) The function of CysC as an inflammatory inducing factor; (4) The ability of CysC to induce autophagy. The combination of these CysC properties provides a well-supported novel biomarker for cerebrovascular diseases.

Effects of kaempferol on learning and memory in rats with chronic cerebral ischemia and possible mechanisms / 中国药理学通报

Aim To investigate the effects and possible mechanisms of kaemperol in the rats with chronic cere-bral ischemia.Methods Chronic cerebral hypoperfu-sion model was produced by permanent occlusion of bi-lateral common carotid arteries (2VO)in rats.After KAE treatment,the rats underwent Morris water maze and prehensile traction test.Neuronal morphology was observed using Nissl and HE staining.The activity of SOD and the content of MDA in brain tissue were de-termined.The DJ-1 protein expression was assayed by Western blot.Results Compared with 2VO model group,KAE significantly improved learning and memo-ry and the grasping ability.In addition,KAE signifi-cantly reduced brain tissue pathological injury induced by 2VO. Furthermore, KAE significantly increased SOD activity and enhanced antioxidant protein DJ-1 ex-pression in brain tissue.Conclusions KAE could sig-nificantly attenuate the cognitive impairment,limb bal-ance dysfunction and pathological injury in rats with chronic cerebral ischemia.The mechanism may be re-lated to improving the antioxidant system in vivo.

Electroacupuncture at the Wangu acupoint suppresses expression of inflammatory cytokines in the hippocampus of rats with vascular dementia / 西安交通大学学报(医学版)

Objective To examine whether electroacupuncture at the Wangu acupoint (GB 12 ) , whose position is similar to the cerebellar fastigial nucleus ,can reduce inflammatory cytokines in the hippocampus of rats with vascular dementia (VD) to provide theoretical evidence for treating VD with electroacupuncture .Methods Healthy Sprague‐Dawley rats ( n=54 ,300 -450 g) were randomly divided into three groups :sham surgery group ,VD group ,and electroacupuncture group .The ethologic scores of VD rats were evaluated and the mRNA expressions of inflammatory cytokines (TNF‐α,IL‐6 and IL‐1β) in the hippocampus were assessed and the hippocampal tissues were observed by hematoxylin‐eosin (HE) staining .Results Compared with VD group ,in electroacupuncture group the rats' learning ability improved significantly and the mRNA expressions of TNF‐α, IL‐6 and IL‐1β decreased . Simultaneously ,the damage extent of nerve cells in the hippocampal tissues decreased , and their morphology recovered to nearly normal .Conclusion Electroacupuncture at the Wangu acupoint can decrease the level of inflammatory cytokines in the hippocampus and reduce the damage extent of nerve cells in the hippocampus ,thus providing a new neuroprotective method for VD .

Correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia in Alzheimer's disease and vascular dementia.

OBJECTIVE: To discuss the correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) and vascular dementia (VD). METHOD: AD cases, VD cases and healthy control cases totaling 237, 255 and 234 were recruited, respectively. The mini-mental state examination (MMSE) was performed to evaluate cognitive impairment. Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were adopted to evaluate BPSD. Apolipoprotein E (APOE) and Low-density lipoprotein receptor-related protein gene (LRP) genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1) Frequencies of APOEε4 allele in AD group and VD group were significantly higher than that of the control (P<0.05); (2) MMSE scores of APOEε4 carriers in AD group and VD group were lower than that of non-APOEε4 carriers in the same group (P<0.05); (3) The proportion of APOEε4 carriers presenting with BPSD in AD group was considerably higher that of non-APOEε4 carriers (P<0.05). CONCLUSION: APOEε4 may be the common risk factor for cognitive impairment in AD and VD and the risk factor for BPSD in AD.

Mechanism arid Treatment of Vascular Dementia with Traditional Chinese Medicine / 国际中医中药杂志

Vascular dementia(VD)is caused by blockage of blood supply in brain leading to damage of brain tissue.The prevention and cure of VD has become an important task with China is stepping into a senile society.Researches of VD trated with traditional Chinese medicine in the recent 10 year are summarized in this paper.