[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.

Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity.

OBJECTIVE: In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe-VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four-week treadmill exercise was performed in the Exe-VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe-VD groups were identified to establish the VD model. Behavior tests (open-field test and novel recognition memory test) were adopted to evaluate anxiety-like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. RESULTS: Our study demonstrated that VD rat exhibited significantly anxiety-like behavior and recognition impairment (p < .01), while treadmill exercise significantly alleviated anxiety-like behavior and improved recognition memory in VD rat (p < .01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p < .05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p < .05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p < .05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe-VD group (p < .05). CONCLUSION: The improvement of VD-associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.

3R Nursing Combined with Dietary and Nutritional Interventions Enhances Self-care Ability in Elderly Patients with Vascular Dementia.

BACKGROUND: Vascular dementia (VD) is an extremely common neurological dysfunction in the elderly population, and greatly affects the patient's ability to take care of themselves. Recent research suggests that VD patients need more targeted and individualized nursing during treatment, so as to enhance cognitive function and therapeutic efficacy. The objective of this study is to observe the effect of reminiscence, reality, and remotivation (3R) nursing combined with dietary and nutritional interventions on elderly patients with VD, so as to provide clinical evidence for the management of VD in older adults. METHODS: 120 elderly VD patients admitted between December 2022 and December 2023 were selected, including 64 cases receiving 3R nursing combined with dietary and nutritional interventions (the research group) and 56 cases receiving routine nursing (the control group). The two groups were compared in terms of neurological function, self-care ability, and nutritional status before and after nursing, as well as nursing compliance. After the completion of the care, patients' quality of life and family satisfaction were investigated. RESULTS: In comparison with the control group, the research group displayed higher scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), greater self-care ability, and higher levels of nutritional proteins and grip strength (p < 0.05). In addition, patients in the research group displayed greater nursing compliance and quality of life of patients, as well as higher family satisfaction (p < 0.05). CONCLUSIONS: 3R nursing combined with dietary and nutritional interventions can effectively improve the neurological function of VD patients and enhance their self-care ability.

[Chinese guidelines for the diagnosis and treatment of vascular cognitive impairment (2024 edition)].

Vascular cognitive impairment (VCI) refers to cognitive impairment primarily mainly caused by cerebrovascular pathologies and their risk factors. It is the second leading cause of cognitive impairment in individuals aged 60 and above in China. Currently, there are no specific treatments for VCI, but early identification and prevention can help reduce the risk of onset and improve patients' prognosis. To raise awareness and attention among clinicians towards VCI and provide guidance for its standardized management, the Chinese Stroke Association Vascular Cognitive Impairment Subcommittee updated and revised the clinical classification, diagnostic procedures, neuropsychological evaluation criteria and imaging evaluation criteria and etc.on the basis of the Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment in China (2019). Through systematic literature reviews, including meta-analysis, systematic review, randomized controlled trials, retrospective studies, clinical case-control studies, etc, evidence and recommendation levels were formulated according to the evaluation and evaluation criteria of recommendation classification, and a total of 8 recommendations were formed on the etiology, clinical classification, clinical manifestations, diagnostic criteria, prevention and treatment of VCI. A standardized diagnostic process for VCI suitable for the clinical practice in China was proposed, aiming at providing guidance for the standardized diagnosis and accurate treatment of VCI.

Transcranial direct current stimulation combined with swimming exercise improves the learning and memory abilities of vascular dementia rats by regulating microglia through miR-223-3p/PRMT8.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia worldwide. Previous studies have proven that transcranial direct current stimulation (tDCS) has potential applications in relieving cognitive impairment in VD animal models. The purpose of this study was to probe the mechanism by which tDCS combined with swimming exercise improves the learning and memory abilities of VD model rats. METHOD: The VD rat model was induced using the permanent bilateral common carotid artery occlusion (2-VO) method; tDCS was applied to the rats and then they took part in swimming exercises. Rat memory, platform crossing time, and platform crossing frequency were analyzed via a water maze experiment. Nerve damage in the cortex and hippocampal CA1 area of the rats was observed using Nissl staining. Western blotting, immunohistochemistry, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT - qPCR) were used to determine the expression of related proteins and genes. The levels of oxidative stress were detected by kits. RESULTS: We demonstrated that VD model rats treated with tDCS combined with swimming exercise exhibited significant improvement in memory, and VD model rats exhibited significantly reduced neuronal loss in the hippocampus, and reduced microglial activation and M1 polarization. tDCS combined with swimming exercise protects VD model rats from oxidative stress through the miR-223-3p/protein arginine methyltransferase 8 (PRMT8) axis and inhibits the activation of the TLR4/NF-κB signaling pathway. CONCLUSION: Our results suggest that tDCS combined with swimming exercise improved the learning and memory ability of VD model rats by regulating the expression of PRMT8 through miR-223-3p to affect microglial activation and M1 polarization.

Low-intensity transcranial ultrasound stimulation improves memory in vascular dementia by enhancing neuronal activity and promoting spine formation.

Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.

The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis.

BACKGROUND: Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. METHOD: Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. RESULTS: In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. CONCLUSION: Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: This study was registered in PROSPERO (CRD42023411720).

Predictors of primary care psychological therapy outcomes for depression and anxiety in people living with dementia: evidence from national healthcare records in England.

BACKGROUND: Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown. AIMS: To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD. METHOD: National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored. RESULTS: People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08-8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15-7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92-0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04-2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96-0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51-0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10-3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09-1.16, P < 0.001) were associated with worse therapy outcomes in PLWD. CONCLUSIONS: Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.

Exercise Improves Cerebral Blood Flow and Functional Outcomes in an Experimental Mouse Model of Vascular Cognitive Impairment and Dementia (VCID).

Vascular cognitive impairment and dementia (VCID) are a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is valid for VCID. Previously, we have reported that remote ischemic postconditioning (RIPostC) during chronic cerebral hypoperfusion (CCH) induced by BCAS increases cerebral blood flow (CBF), improves cognitive function, and reduces white matter damage. We hypothesized that physical exercise (EXR) would augment CBF during CCH and prevent cognitive impairment in the BCAS model. BCAS was performed in C57/B6 mice of both sexes to establish CCH. One week after the BCAS surgery, mice were randomized to treadmill exercise once daily or no EXR for four weeks. CBF was monitored with an LSCI pre-, post, and 4 weeks post-BCAS. Cognitive testing was performed for post-BCAS after exercise training, and brain tissue was harvested for histopathology and biochemical test. BCAS led to chronic hypoperfusion resulting in impaired cognitive function and other functional outcomes. Histological examination revealed that BCAS caused changes in neuronal morphology and cell death in the cortex and hippocampus. Immunoblotting showed that BCAS was associated with a significant downregulate of AMPK and pAMPK and NOS3 and pNOS3. BCAS also decreased red blood cell (RBC) deformability. EXR therapy increased and sustained improved CBF and cognitive function, muscular strength, reduced cell death, and loss of white matter. EXR is effective in the BCAS model, improving CBF and cognitive function, reducing white matter damage, improving RBC deformability, and increasing RBC NOS3 and AMPK. The mechanisms by which EXR improves CBF and attenuates tissue damage need further investigation.

Effects of electroacupuncture on the microvascular structure and related protein expression in the hippocampus of vascular dementia rats. / ç”µé’ˆå¯¹è¡€ç®¡æ€§ç—´å‘†å¤§é¼ æµ·é©¬å¾®è¡€ç®¡ç»“æž„å’Œç›¸å ³è›‹ç™½è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To explore the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the microvascular structure and related protein expression in the hippocampus of vascular dementia (VD) rat model, and to investigate the mechanism of EA in the treatment of VD. METHODS: A total of 24 SD rats were randomly divided into sham operation, model, EA, and oxiracetam groups, with 6 rats in each group. Multiple cerebral infarction method was used to establish VD model. In the EA group, EA was applied to GV20 and GV24 for 30 min, once daily for 14 days. Rats in the oxiracetam group were treated with oxiracetam (50 mg/kg) by intraperitoneal injection, and the course of treatment was the same as that in the EA group. Learning and memory ability were evaluated by using Morris water maze test and new object recognition experiment. The cerebral blood flow was detected by laser doppler. The microvascular structure in the hippocampus was observed by transmission electron microscopy. The expression of vascular structure related proteins of platelet-derived growth factor receptor (PDGFR)-ß, platelet endothelial cell adhesion molecule-1(CD31), neural cadherin N-Cadherin, Zonula occludens protein-1(ZO-1) in the hippocampus were measured by Western blot. RESULTS: Compared with the sham operation group, the rats in the model group had a significant increase in time of first crossing the platform, a significant decrease in the number of crossing platform and the new object preference index (P<0.05), a significant decrease in cerebral blood flow (P<0.05), and a significant increase in the brain weight (P<0.05). The structure boundary of pericyte and endothelial cells in the microvessels of the hippocampal CA1 area of model group was blurred, accompanied by obvious edema around the vessels and the reduction of tight junctions. The protein expression levels of PDGFR-ß, CD31, N-Cadherin, ZO-1 were significantly decreased in the model group compared with those in the sham operation group (P<0.05). Compared with the model group, the time of first crossing the platform of rats in the EA and oxiracetam group was shortened, the number of crossing platform were increased (P<0.05), the cerebral blood flow was increased (P<0.05), the brain weight was decreased (P<0.05), the morphology and structure of pericyte and endothelial cells in the microvessels of hippocampal CA1 area were intact, accompanied by the increase of tight junctions. Additionally, Compared with the model group, the EA group had a significant increase in the new object preference index (P<0.05), the protein expression levels of PDGFR-ß, CD31, ZO-1 in the EA group were increased (P<0.05), and the expression of PDGFR-ß, N-Cadherin, ZO-1 in the oxiracetam group were increased (P<0.05). CONCLUSIONS: EA at GV20 and GV24 can improve the learning and memory ability of VD rats, and the mechanism may be related to the repair of microvascular structures and improvement of cerebral blood flow.

[Effect of moxibustion on inositol requiring enzyme 1 / X-box binding protein 1 pathway in hippocampal CA1 region of rats with vascular dementia].

OBJECTIVE: To observe the effect of moxibustion at Governor Vessel acupoints on inositol requiring enzyme 1 （IRE1） / X-box binding protein 1 （XBP1） pathway in hippocampal CA1 region of rats with vascular dementia （VD）, so as to explore its mechanisms in the treatment of VD. METHODS: Male SD rats were randomly divided into normal, sham operation, model, moxibustion （Moxi） and medication groups （n=12）. The VD model was established by permanent ligation of bilateral common carotid arteries. For rats of the Moxi group, mild moxibustion was given to "Baihui" （GV20）, "Dazhui" （GV14） and "Fengfu" （GV16） for 20 min each point, once a day for consecutive 6 days per week, for a total of 4 weeks. For rats of the medication group, intragastric perfusion of nimodipine was given 3 times each day with total dose of 2 mg•kg-1•d-1 for 4 weeks. Morris water maze test was used to detect the learning and memory ability of rats before and after modeling as well as after intervention. The apoptosis rate of nerve cells in hippocampal CA1 region was detected by TUNEL staining. The proteins and mRNA expression levels of IRE1, XBP1, B-cell lymphoma/leukemia-2 （Bcl-2）, Bcl-2 associated X protein （Bax） in hippocampal CA1 region were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the sham operation group, the average escape latency was significantly prolonged （P<0.01）, the number of times crossing the original platform was significantly reduced （P<0.01）, the apoptosis rate of nerve cells in hippocampal CA1 region was significantly increased （P<0.01）, the proteins and mRNA expression levels of IRE1, XBP1 and Bax were significantly increased （P<0.01）, and the expression levels of Bcl-2 protein and mRNA were significantly decreased （P<0.01） in rats of the model group. After treatment, compared with the model group, the average escape latency was significantly shortened （P<0.01）, the number of times crossing the original platform was increased （P<0.05）, the apoptosis rate of nerve cells in hippocampal CA1 region was significantly decreased （P<0.01）, the protein and mRNA expression levels of IRE1, XBP1 and Bax were decreased （P<0.05, P<0.01）, and the expression levels of Bcl-2 protein and mRNA were increased （P<0.05, P<0.01） in rats of the Moxi group and medication group. There was no significant difference in the above indexes between the Moxi group and the medication group. CONCLUSION: Moxibustion at the acupoints of Governor Vessel can improve the cognitive function of VD rats, and its mechanism may be related to regulating IRE1/XBP1 pathway, inhibiting the release of pro-apoptotic protein Bax, increasing the expression of anti-apoptotic protein Bcl-2, and thus inhibiting the apoptosis of hippocampal nerve cells.

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association.

Lacunar infarcts and vascular dementia are important phenotypic characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the most common inherited cerebral small vessel disease. Individuals with the disease show variability in the nature and onset of symptoms and rates of progression, which are only partially explained by differences in pathogenic mutations in the NOTCH3 gene. Recognizing the disease early in its course and securing a molecular diagnosis are important clinical goals, despite the lack of proven disease-modifying treatments. The purposes of this scientific statement are to review the clinical, genetic, and imaging aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, contrasting it with other inherited small vessel diseases, and to provide key prevention, management, and therapeutic considerations with the intent of reducing practice variability and encouraging production of high-quality evidence to support future treatment recommendations.

To Explore the Safety of 3R Nursing and Dietary Nutrition Intervention in Elderly Patients with Vascular Dementia and the Effect of Improving the Self-Care Ability of Patients.

Objective: Exploring the application safety of 3R nursing and dietary nutrition intervention in elderly vascular dementia, as well as the application value of improving patients' self-care ability in elderly vascular dementia. Method: 120 elderly patients with vascular dementia in our hospital from August 2020 to June 2022 were selected as the research subjects and divided into an observation group (n = 60) and a control group (n = 60) using a random number table method. The control group received routine care+3R care, while the observation group received dietary and nutritional interventions on the basis of the control group. Compare the Mini Mental State Examination (MMSE), Neuropsychiatric Inventory Questionnaire (NPI-Q) before and after intervention between two groups, and investigate the Activities of Daily Living (ADL), Quality of Life Alzheimer's Disease (QOL-AD) Score with the Simplified Fugl Meyer Motor Function Rating Scale (FMA) and calculate nursing satisfaction. Result: After intervention, the MMSE score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P < .05). The NPI-Q score was significantly lower than that of the control group, with a statistically significant difference (P < .05). After intervention, the ADL score of the observation group was significantly lower than that of the control group, with a statistically significant difference (P < .05). The QOL-AD score was significantly higher than that of the control group, with a statistically significant difference (P < .05). After intervention, the FMA score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P < .05). In addition, the incidence of adverse reactions in the observation group was significantly lower than that in the control group, with a statistically significant difference (P < .05). There was no statistically significant difference in the number of people who were basically satisfied and needed improvement between the two groups (P > .05). The observation group had significantly more people who were very satisfied than the control group, and the number of people who were dissatisfied was significantly lower than the control group, with a statistically significant difference (P < .05). Conclusion: 3R nursing with diet and nutrition intervention improves safety, self-care ability, cognitive function, and nursing satisfaction in elderly patients with vascular dementia, suggesting its potential for clinical implementation.

["Huayu Tongluo" moxibustion improves learning-memory ability and promotes myelin regeneration by regulating Sonic Hedgehog signaling pathway in vascular dementia rats].

OBJECTIVE: To investigate the effect of "Huayu Tongluo" (resolving blood stagnation to dredge meridian-collaterals) moxibustion on remyelination and Sonic Hedgehog (Shh) signaling pathway in the corpus callosum of vascular dementia (VD) rats, so as to explore its mechanisms underlying improvement of VD. METHODS: Male Wistar rats were randomized into sham-operation, model, medication and moxibustion groups, with 12 rats in each group.The VD model was established by bilateral common carotid artery occlusion. Moxibustion was applied to "Shenting"(GV24), "Baihui"(GV20) and "Dazhui"(GV14) for 20 min once a day, 7 d as a treatment course, for 3 courses, with one day's rest between every two courses. Rats of the medication group were treated by gavage of 10 mg/kg of chloromastine solution once a day, and the course of treatment was the same as that of the moxibustion group. The rat's learning-memory ability was assessed by Morris water maze test (escape latency). The neurological deficits were evaluated by using Longa's scale.The mRNA and protein expressions of Shh and Gli1 in the corpus callosum were measured by quantitative real-time fluorescence PCR and Western blot, separately. The ultrastructure of the myelin sheath and myelinated axons was observed under transmission electron microscopy (TCM). RESULTS: Compared with the sham-operation group, the neurologic score and escape latency were significantly increased and prolonged (P<0.01), and the mRNA and protein expression levels of Shh and Gli1 and the number of myelinated axons were obviously decreased in the model group (P<0.01). In comparison with the model group, the escape latency was apparently shortened (P<0.05), while the mRNA and protein expression levels of Shh and Gli1 as well as the number of myelinated axons were strikingly increased in both moxibustion and medication groups (P<0.01). Results of TCM showed that in the model group, the arrangement of myelin coil structures was sparse and fuzzy, and some structures were bulged and disbanded. The oligodendrocytes were irregular, and the number of myelin sheath was rare. These situations were relatively milder in both moxibustion and medication groups. CONCLUSION: "Huayu Tongluo" moxibustion can promote the differentiation and maturation of oligodendrocyte precursor cells after cerebral ischemia by regulating the expressions of Shh and Gli1 in Shh signaling pathway, thus promoting the regeneration of cerebral white matter myelin sheaths in VD rats, which may contribute to improving learning-memory ability.

Can acupuncture reverse oxidative stress and neuroinflammatory damage in animal models of vascular dementia?: A preclinical systematic review and meta-analysis.

BACKGROUND: Vascular dementia is a cognitive dysfunction syndrome caused by cerebral vascular factors such as ischemic stroke and hemorrhagic stroke. The effect of acupuncture on vascular dementia models is ambiguous, and there is controversy about whether acupuncture has a placebo effect. Oxidative stress and inflammation are the most essential mechanisms in preclinical studies of vascular dementia. However, there is no meta-analysis on the mechanism of vascular dementia in animal models. It is necessary to explore the efficacy of acupuncture through Meta-analysis of preclinical studies. METHODS: Three major databases, PubMed, Embase and Web of Science (including medline), were searched in English until December 2022.The quality of the including literature was assessed using SYRCLE's risk of bias tool. Review Manager 5.3 was used to statistically summarize the included studies and the statistical effect values were expressed by SMD. The outcomes included: behavioral tests (escape latency, number of crossings), pathological sections (Nissl and TUNEL staining), oxidative stress markers (ROS, MDA, SOD, GSH-PX) and neuroinflammatory factors (TNF-α, IL-1ß, IL-6). RESULTS: A total of 31 articles were included in this meta-analysis. The results showed that the escape latency, the contents of ROS, MDA, IL-1ß, and IL-6 were decreased, and the contents of SOD and Nissl-positive neurons were increased in the acupuncture group as compared with the non-group (P < .05). Compared with the impaired group, the acupuncture group also had the above advantages (P < .05). In addition, the acupuncture group also increased the number of crossings and GSH-PX content, and decreased the expression of TUNEL-positive neurons and TNF-α (P < .05). CONCLUSIONS: From behavioral tests to slices and pathological markers in animal models of vascular dementia, it can be proved that acupuncture is effective in targeting oxidative stress and neuroinflammatory damage, and acupuncture is not a placebo effect. Nevertheless, attention needs to be paid to the gap between animal experiments and clinical applications.

Clinical Effect of Shibing Xingnao Granules on Vascular Dementia Patients and Its Effect on Serum Neuronal Apoptosis Molecules.

It was intended to study the clinical effect of Shibing Xingnao Granules on patients with vascular dementia (VD) and to explore its effect on serum neuronal apoptosis molecule levels in VD patients. For this purpose, 78 VD patients, as research objects, were grouped into a control group (acupuncture therapy) and an observation group (acupuncture therapy + Shibing Xingnao Granules) using the random number table method, with 39 cases per group. The clinical effect, cognitive function, neurological function, activity of daily living (ADL) score, and serum B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), as well as Caspase-3 (Casp3) levels in two groups were observed. Results showed that the markedly effective rate (MER) (82.05%) and total effective rate (TER) (100%) in the observation group were higher than the control group (56.41%, 92.31%) (P<0.05). After treatment, the Mini-mental State Examination (MMSE) score, the distributions of mild VD and normal patients, ADL score, and Bcl-2 level were higher in the observation group than in the control group. National Institutes of Health Stroke Scale (NIHSS) score, Bax, and Casp3 levels were lower in the observation group (P<0.05). The conclusion was that Shibing Xingnao Granules could further enhance the therapeutic effect of VD patients, and could increase Bcl-2 level and reduce Bax and Casp3 levels.

Vascular dementia subtypes, pathophysiology, genetics, neuroimaging, biomarkers, and treatment updates along with its association with Alzheimer's dementia and diabetes mellitus.

Dementia is a chronic progressive cognitive decline illness that results in functional impairment. Vascular dementia (VaD), second only to Alzheimer's disease (AD), is one of the most prevalent forms of dementia in the elderly (aged over 65 years), with a varied presentation and unpredictable disease development caused by cerebrovascular or cardiovascular illness. To get a better understanding of the changes occurring in the brain and to drive therapy efforts, new biomarkers for early and precise diagnosis of AD and VaD are required. In this review, Firstly, we describe the subtypes of vascular dementia, their clinical features, pathogenesis, genetics implemented, and their associated neuroimaging and biomarkers, while describing extensively the recent biomarkers discovered in the literature. Secondly, we describe some of the well-documented and other less-defined risk factors and their association and pathophysiology in relation to vascular dementia. Finally, we follow recent updates in the management of vascular dementia along with its association and differentiation from Alzheimer's disease. The aim of this review is to gather the scattered updates and the most recent changes in blood, CSF, and neuroimaging biomarkers related to the multiple subtypes of vascular dementia along with its association with Alzheimer's dementia and diabetes mellitus.

High-intensity interval training improves cognitive impairment of vascular dementia rats by up-regulating expression of brain-derived neurotrophic factor in the hippocampus.

The present study aims to investigate the effect and its potential mechanism of high-intensity intermittent training (HIIT) on cognitive function in vascular dementia (VD) rats. The VD rats with the cognitive impairment were induced by bilateral common carotid artery occlusion (BCCAO), and the ones in the moderate-intensity continuous training (MICT) group and HIIT group received MICT or HIIT for 5 consecutive weeks, respectively. The swimming speed, endurance, and grip strength of rats were all measured after training. The effect and mechanisms of HIIT on ameliorating the cognitive dysfunction were further evaluated by the Morris water maze test, histomorphological analysis, and Western blot analysis. As a result, no significant difference in motor function between VD rats and sham rats was observed. After 5-week HIIT, the motor function of VD rats was significantly enhanced. The results of the Morris water maze test revealed that HIIT significantly reduced escape latency as well as distance to find the platform compared with the sedentary control group (SED group), indicating the improvement in cognitive function. In addition, the hippocampal tissue damage of VD rats measured by H&E staining was markedly ameliorated after 5-week HIIT. Moreover, brain-derived neurotrophic factor (BDNF) expression level in the cerebral cortex and hippocampus tissue detected by Western blot were significantly up-regulated in HIIT group compared to SED group and MICT group. In conclusion, HIIT can improve BCCAO-induced cognitive impairment via up-regulating BDNF expression in VD rats.

Neuroprotective mechanism of human umbilical cord mesenchymal stem cell-derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia.

Vascular dementia (VaD) is a prevalent cause of dementia after Alzheimer's disease. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-Evs) are critical for VaD treatment. We explored the mechanism of hUCMSC-Evs in VaD. VaD rat model was established by bilateral common carotid artery ligation and hUCMSC-Evs were extracted. VaD rats were injected with Evs through the tail vein. Rat neurological scores, neural behaviors, memory and learning abilities, brain tissue pathological changes, and neurological impairment were evaluated by Zea-Longa method, Morris water maze tests, HE staining, and ELISA (through acetylcholine [ACH] and dopamine [DA] assessment). Microglia M1/M2 polarization was detected by immunofluorescence staining. Pro-/anti-inflammatory factor levels in brain tissue homogenate, oxidative stress-related indicators, and p-PI3K, PI3K, p-AKT, AKT, and Nrf2 protein levels were determined by ELISA, kits, and Western blot. VaD rats were jointly treated with PI3K phosphorylation inhibitor Ly294002 and hUCMSC-Evs. VaD rats manifested increased neurological function injury scores, decreased cognitive function and learning ability, abnormal brain structure, obvious inflammatory infiltration, diminished ACH and DA levels, increased microglial cells and M1-polarized cells, M1/M2 polarization ratio, inflammation, and oxidative stress. hUCMSC-Evs alleviated the neurological damage of VaD rats, inhibited M1 polarization, inflammation, and oxidative stress of microglial cells in brain tissues of VaD rats, and activated the PI3K/AKT/Nrf2 pathway. Ly294002 partially averted the effects of hUCMSC-Evs on microglial polarization, inflammation, and oxidative stress. Briefly, hUCMSC-Evs activated the PI3K/AKT/Nrf2 pathway and inhibited microglial M1 polarization, inflammation, and oxidative stress, thus protecting VaD rat nerve functions.

Electroacupuncture inhibits hippocampal neuronal apoptosis and improves cognitive dysfunction in mice with vascular dementia via the JNK signaling pathway.

BACKGROUND: Electroacupuncture (EA) has been shown to reduce cognitive impairment in vascular dementia (VaD) patients. However, the mechanism of action remains unknown. OBJECTIVE: The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in apoptosis. Herein, we focused on whether EA can inhibit apoptosis and alleviate cognitive impairment by regulating the JNK signaling pathway using a mouse model of VaD induced by modified bilateral common carotid artery occlusion (BCCAo). METHODS: In experiment I, 60 mice were randomly divided into a Sham group, BCCAo group, BCCAo + EA group, BCCAo + Sham-EA group, BCCAo + SP group (receiving the selective JNK inhibitor SP600125) and BCCAo + SP + EA group. Morris water maze tests, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining and flow cytometry were used to evaluate the effect of the EA intervention on VaD. In experiment II, 30 mice were randomly divided into a Sham group, BCCAo group, BCCAo + EA group, BCCAo + SP group and BCCAo + SP + EA group. Western blotting and real-time reverse transcription polymerase chain reaction were used to detect protein and mRNA expression of key factors in the JNK signaling pathway in the hippocampus. RESULTS: EA, SP600125 and EA + SP600125 significantly inhibited hippocampal apoptosis and improved cognitive impairment in VaD model mice. There were no significant differences between the BCCAo group and the BCCAo + Sham-EA group. EA, EA + SP600125 and SP600125 inhibited the phosphorylation of JNK and caspase-3. EA and EA + SP600125 promoted protein and mRNA expression of B-cell lymphoma 2 (Bcl-2) in the hippocampus of VaD mice and inhibited protein and mRNA expression of activator protein (AP)-1, p53 and Bax. CONCLUSION: EA can reverse cognitive deficits and inhibit hippocampal neuronal apoptosis in VaD model mice, at least partially through inhibition of the JNK signaling pathway and regulation of apoptosis signals.