OBJECTIVE: To observe the effects of moxibustion at Yongquan（KI 1） on the cognitive function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency. METHODS: Eighty-four patients with post-stroke cognitive impairment of kidney essence deficiency were randomly divided into an observation group（42 cases，1 case dropped off）and a control group（42 cases，1 case dropped off）.The control group was treated with medication，electroacupuncture，rehabilitation training and repetitive transcranial magnetic stimulation（rTMS）；on the basis of the treatment as the control group，moxibustion at bilateral Yongquan（KI 1）was adopted in the observation group.Both groups were treated once a day，5 days a week with 2-day interval，4 weeks were required. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, Fugl-Meyer assessment-lower extremity (FMA-LE) score, Berg balance scale (BBS) score, functional independence measure (FIM) score, modified fall efficacy scale (MFES) score and scale for the differentiation of syndromes of vascular dementia (SDSVD) score before and after treatment were observed in the two groups. RESULTS: After treatment，the MoCA, MMSE, FMA-LE, BBS, FIM and MFES scores were higher than those before treatment in both groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment，the SDSVD scores were lower than those before treatment in both groups (P< 0.05), and the SDSVD score in the observation group was lower than that in the control group (P< 0.05). CONCLUSION Moxibustion at Yongquan（KI 1） can improve the cognitive function and motor and balance function of lower limbs in patients with post-stroke cognitive impairment of kidney essence deficiency，reduce the risk of fall and improve the quality of life.
Humans ; Cognition ; Cognitive Dysfunction/therapy* ; Dementia, Vascular ; Kidney ; Lower Extremity ; Moxibustion ; Quality of Life ; Stroke/complications*

Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aβ injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.
Humans ; Dementia, Vascular/drug therapy* ; Vascular Endothelial Growth Factor A ; NF-kappa B/metabolism* ; Antioxidants ; Brain Ischemia ; Cholinergic Agents

Humans ; Dementia, Vascular ; Proteomics ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Cognition

OBJECTIVE: To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD. METHODS: A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. RESULTS: There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01). CONCLUSION Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.
Acupuncture Therapy ; Animals ; Dementia, Vascular/therapy* ; Interferon-gamma ; Interleukin-10 ; Interleukin-4 ; Neuroinflammatory Diseases ; Rats ; Rats, Wistar ; Th2 Cells ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.
Animals ; Dementia, Vascular/therapy* ; Electroacupuncture ; Hippocampus/metabolism* ; Immunity ; Myeloid Differentiation Factor 88 ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4/metabolism*

In light of the tremendous number of patients with vascular dementia in China, it is of great significance for the treatment of this disease to summarize related research focuses. In this study, articles on the treatment of vascular dementia, which were included in CNKI and Web of Science from January 1, 2012 to December 31, 2021, were analyzed. Specifically, CiteSpace 5.7.R2 was employed to visualize nationalities of authors, author affiliations, authors, keywords, and journals, and dissect the status quo and trend of research on the treatment of this disease. On this basis, the research focuses and evolution were elucidated. The findings are expected to serve as reference for the future research. Finally, 2 579 Chinese articles and 453 English articles were included. The annual number of published articles showed an upward trend. Authors from China published most papers and England had the highest centrality value. HU Yue-qiang and LIU Cun-zhi respectively published the most Chinese and English articles. Guangxi University of Chinese Medicine and Capital Medical University respectively topped the author affiliations in the number of published Chinese and English articles. Among the English journals, Anal Biochem and Stroke separately boasted the highest centrality value and the highest cited frequency. The analysis of keywords in the Chinese articles suggested that most studies on the treatment of vascular dementia focused on the observation of patients' mobility after treatment. Moreover, as for the therapeutic method, western medicine, as well as the Chinese medicine and acupuncture frequently attracted the attention of scholars. Basic research highlighted the oxidative stress, angiogenesis, and apoptosis. According to the analysis result of keywords in English articles on treatment of vascular dementia, the focus was the improvement of the memory function of patients with vascular dementia. As to the therapeutic method, drug therapy was frequently studied compared with other methods. The basic research focused on autophagy, nerve regeneration, and oxidative stress. This study concludes that the future research trend might be the combination of Chinese and western medicine in the treatment of vascular dementia.
Humans ; China ; Dementia, Vascular/therapy* ; Publications ; Acupuncture Therapy

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.
Dementia, Vascular/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Injections ; Medicine ; Salvia miltiorrhiza

Acetylcholinesterase ; Activities of Daily Living ; Acupuncture Points ; Acupuncture Therapy ; Dementia, Vascular/therapy* ; Humans ; Moxibustion ; Vascular Endothelial Growth Factor A

OBJECTIVE: To observe the clinical efficacy of early acupuncture for vascular dementia (VD) after cerebral infarction, and explore its possible mechanism. METHODS: A total of 120 patients with VD after cerebral infarction were randomized into an acupuncture combined with medication group (60 cases, 1 case dropped off) and a western medication group (60 cases, 1 case dropped off). In the western medication group, oxiracetam capsules were given orally, 2 capsules each time, 3 times a day. On the basis of the treatment as the western medication group, RESULTS: The total effective rate was 89.8% (53/59) in the acupuncture combined with medication group, which was superior to 76.3% (45/59) in the western medication group ( CONCLUSION Early acupuncture could improve cognitive function and activities of daily living in patients with VD after cerebral infarction, its mechanism may be related to improving the blood flow velocity of MCA, promoting blood circulation, and improving cerebral perfusion.
Activities of Daily Living ; Acupuncture Points ; Acupuncture Therapy ; Cerebral Infarction/therapy* ; Cognition ; Dementia, Vascular/therapy* ; Humans ; Treatment Outcome

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.
Animals ; Apoptosis ; Cognition ; Dementia, Vascular/therapy* ; Hippocampus ; Moxibustion ; Neurons ; Rats ; Rats, Sprague-Dawley