Mendelian Randomization Study of Causal Relationship between Inflammatory Factors and Vascular Dementia and Chinese Herbal Medicines Screening for Prevention and Treatment

Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.

Transcatheter treatment of atherosclerotic lesions of the brain complicated by vascular dementia development

The research focuses on the effectiveness of transluminal laser revascularization of the brain in the treatment of atherosclerotic lesions accompanied by vascular dementia development. 1125 patients aged from 29 to 81 (average age 75) suffering from various kinds of atherosclerotic lesions of cerebral vessels were examined during the research. The examination plan included: computed tomography of the brain (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), cerebral multi-gated angiography (MUGA). 665 (59.11%) patients suffered from diseases accompanied by the development of vascular dementia. To perform transcatheter treatment, 639 patients were selected: Group 1 (CDR-1)—352 patients, Group 2 (CDR-2)—184 patients, Group 3 (CDR-3)—103 patients. To conduct revascularization of main intracranial arteries high-energy laser systems were used;for revascularization of the distal intracranial branches low-energy laser systems were used. The clinical outcome depended on the severity of dementia and the timing of the intervention. A good clinical outcome in Group 1 was obtained in 281 (79.82%) cases, in Group 2 in 81 (44.02%) cases, in Group 3 in 9 (8.73%) cases. A satisfactory clinical outcome in Group 1 was obtained in 53 (15.34%) cases, in Group 2 in 62 (33.70%) cases, in Group 3 in 31 (30.09%) cases. A relatively satisfactory clinical outcome in Group 1 was obtained in 17 (4.83%) cases, in Group 2 in 41 (22.28%) cases, in Group 3 in 63 (61.16%) cases. No negative effect was observed after the intervention. Evaluating the data obtained it can be concluded that the method of transluminal laser revascularization of cerebral blood vessels is an effective one for the treatment of atherosclerotic lesions of the brain accompanied by dementia.

Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion

Panax ginseng is a slow-growing perennial plant.Panax ginseng extract has numerous biological activities,including antitumor,anti-inflammatory and antistress activities.Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment.In this study,we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion,a wellknown model of vascular dementia.The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract.Morris water maze and balance beam tests were used to evaluate memory deficits and motor function,respectively.Protein quantity was used to evaluate cholinergic neurons.Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells.Western blot assay was used to evaluate protein levels of vascular endothelial growth factor,basic fibroblast growth factor,Bcl-2 and Bax.Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and b FGF protein expression in the hippocampal CA3 area.Furthermore,Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells,and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression.The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine,a commonly used drug for the treatment of vascular dementia.These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion,and therefore might have therapeutic potential for preventing and treating the disease.

Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride：P300 event related potential

Acupuncture can be used to treat various nervous system diseases.Here,168 vascular dementia patients were orally administered donepezil hydrochloride alone（5 mg/day,once a day for 56 days）,or combined with acupuncture at Shenting（DU24）,Tianzhu（BL10）,Sishencong（Extra）,Yintang（Extra）,Renzhong（DU26）,Neiguan（PC6）,Shenmen（HT7）,Fengchi（GB20）,Wangu（GB12） and Baihui（DU20）（once a day for 56 days）.Compared with donepezil hydrochloride alone,P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture.Mini-Mental State Examination score was also higher.Moreover,these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture.These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia,and exerts neuroprotective effects against vascular dementia.

Microbleeds in fronto-subcortical circuits are predictive of dementia conversion in patients with vascular cognitive impairment but no dementia

Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Association of severity and sex with vasoactive substance and sexual hormone level in patients with vascular dementia in the type of kidney asthenia and blood stasis syndrome

BACKGROUND: Kidney asthenia is the basic cause of the development of vascular dementia (VD). Kidney asthenia lasting for a long time will result in blood stasis. Also, the cause of VD may have relationships with endothelin (ET), nitric oxide (NO), homocysteine (HCY), estrogen (E2), and testosterone (T). OBJECTIVE: To observed clinical curative effect of the kidney tonic, pancreas tonic, and blood tonic with promoting blood circulation components in treating kidney asthenia with blood stasis syndrome of VD. DESIGN: Case controlled study. SETTING: Geriatric Institute of Integrated Medicine, Fujian College of Traditional Chinese Medicine. PARTICIPANTS: A total of 70 patients, including 39 males and 31 females aged 60-80 years, were selected from Department of Neurology, Pingshan Hospital from May 2000 to September 2002. Diagnostic criteria were used for probable VD of the American Psychiatric Association. Diagnostic and Statistical of Manual of Mental Disorder, 4th ed (DSM-Ⅳ), 1994 revised, mini-mental state examination (MMSE), and criteria of kidney asthenia with blood stasis with mixed weak and sthenia syndrome of Guidelines of Clinical Research of New Chinese Medicine in Treating Dementia. According to score of kidney asthenia with blood stasis syndrome, they were classified to three groups: mild (n =22), moderate (n =33) and severe (n =15). All of them with complete chest X-Ray, ECG, blood chemistry and other related examinations, exclusive of cardiovascular, liver, kidney diseases, homeopathy and psychiatry diseases. And hereby we also select 30 normal people as the comparing group, having no substantial diseases in heart, brain, kidney, liver, lung and other main organic systems after medical examination. Of this group, 11 were males and 19 were females, ranging from 62 years old to 78 years old. There were no obvious differences between the above two groups in sex, age, and education level after statistical analysis. All patients observed in Pingxi Hospital, Fuzhou, from May 2000 to September 2002. METHODS: ① According to the diagnoses standard of blood stasis syndrome: 0-89: The increase in score indicated that blood stasis syndrome was getting serious. ② According to MMSE: All the test samples were evaluated, those with scores of 0-30, in which the non-educated ≤ 17, primary school ≤ 20, above middle school ≤ 24 were categorized. ③ Testing all sample's ET, E2 and T by using radioimmunoassay, the RIA kits were provided by Scientific and Technological Development Center of General Hospital of PLA. ④ Testing the level of NO by using colorimetic method. ⑤ Testing the level of HCY by using Enzyme-linked Immunoassay. ⑥ Meanwhile, analyzing the blood stasis score by comparing with every standard. The differences of data were compared by using t test and F test. MAIN OUTCOME MEASURES: ① Blood plasma ET, blood serum NO, HCY, E2 and T. ② The analyzing results obtained from comparing score of blood stasis with every indicators. RESULTS: The result analysis was including of both the 70 patients of VD with kidney asthenia and blood stasis and compared group consist of 30 healthy people. ① ET, NO, HCY and ET/NO: The levels of ET, HCY and ET/NO were increasing with pathography, while the levels of ET, NO, HCY and ET/NO were decreasing with the pathography, and the difference in statistics was significant (P < 0.01). ② The level of E2 and T: The levels of both E2, T and E2/T for male VD patients were (67.72±12.18) pg/L and (351.58±155.02) ng/L, 0.24±0.12 respectively, which were higher than the compared group [(53.96±16.13) pg/L, (471.83±143.99) ng/L, 0.12±0.00, P < 0.05]. The level of E2 in the female VD patients was lower than the compared group [(34.23±10.99), (44.81±14.65) pg/L, P < 0.05]. ③ The relationship between the score of blood stasis and each indicators: The levels of ET, ET/NO and HCY had significant positive relationship with blood stasis mark (r = 0.352, 0.754, 0.347, P < 0.05-0.01), obvious negative relationship with NO (r =-0.528, P < 0.01) and no clear relationship with female E2/T and male E2/T (r = -0.210, 0.04, P > 0.05). CONCLUSION: ① The levels of ET, HCY and ET/NO are increasing with pathography, while the level of NO is decreasing, which may be the evidence that the possibility of VD pathography may have relationship with the indicators above. ② The level of E2 increase in male's VD patients, and decrease in male's. And the decrease of the female may have relationship with the VD.

Usefulness of the Japanese version of Rapid Dementia Screening Test for mild cognitive impairment in older patients with cardiovascular disease:a cross-sectional study

BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test(RDST-J), which is a simple screening tool for identifying cognitive decline.METHODS This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD.Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment(Mo CA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic(ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a Mo CA-J score of ≤ 25 points.RESULTS The study included 78 patients(mean age: 77.2 ± 8.9 years). The RDST-J and Mo CA-J scores were strongly correlated(r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899(95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia(RDST-J score of ≤ 4 points).CONCLUSIONS The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.

EFFECT OF AURICULAR ACUPUNCTURE ON THE LEARNING AND MEMORY AND bcl-2 EXPRESSION IN VASCULAR DEMENTIA RATS

Objective: To study the effect of auricular acupuncture on dysmnesia and the relationship between the memory improvement and bcl 2 protein expression in vascular dementia (VD) rats. Methods: Forty Wistar rats were randomized into control group, VD group, acupuncture+VD group and pseudo operation group, with 10 cases in each group. Rat VD model was established by using 4 vessel occlusion method. Otopoint "Nao" point and "Shen"(MA SC) were punctured, once daily continuously for 15 days. The rats’ memory capability was tested with Y maze method and bcl 2 expression of the brain tissues displayed by immunohistochemical method and measured using MIAS 2000 Image Analyzer. Results: Results showed that the scores of control group, VD group and acupuncture+VD group before operation were 5.68±1.29, 6.07±1.67 and 5.86±1.74 respectively, while following auricular acupuncture treatment, the scores of the 3 groups were 5.81±1.51, 18.06±2.68 and 8.31±1.85 separately, suggesting that the VD rat’s learning and memory abilities in acupuncture+VD group were raised apparently in comparison with those of VD group (P<0.01). In control, VD and acupuncture+VD group, bcl 2 immuno reaction positive neurons in CA 1 area of the hippocampus were 14.31±4.87, 28.67±5.63 and 65.74±8.19 respectively, displaying that the improvement of learning and memory abilities caused by auricular acupuncture treatment may be related to the up regulation of bcl 2 expression (an inhibitory gene of apoptosis). In comparison with control group, the loss of neurons in the pyramidal cell layer of the hippocampal CA 1 area of VD group was more severe, while that of acupuncture group was markedly lighter. Conclusion: Auricular acupuncture of otopoint "Nao" point and "Shen"(MA SC) can raise the learning and memory abilities of VD rats, which may be realized by its inhibitory effect on apoptosis and the protection action on ischemic hippocampal neurons.

A COMPARATIVE STUDY ON THE TREATMENT OF VASCULAR DEMENTIA BY PUNCTURING BAIHUI (GV20), SHUIGOU (GV26) AND SHENMEN (HT7)

Objective: To observe the relative specialty of the therapeutic effect of acupuncture of Baihui (百会 GV 20), Shuigou (水沟 GV 26) a nd Shenmen (神门 HT 7) in the treatment of vascular dementia (VD) patients. Methods: F ifty VD patients were randomly divided into routine treatment group (control gro up), Baihui (GV 20) group (GV 20 group), Shuigou (GV 26) group (GV 26 gr oup), Shenmen (HT 7) group (HT 7 group) a nd GV 20+GV 26+HT 7 group (joint treatment group), with 10 cases in ea ch group. In control group, acupoints used were Jianyu (肩NFDA1 LI 15), Quchi (曲池 L I 11), Waiguan (外关 TE 5), etc. (which were also used in the other four groups) on the paralyzed side. The treatment was conducted once a day except weekends, 20 session s all together. Clinical Dementia Rating Scale (CDR), Mini-Mental State Examin at ion (MMSE) test, Blessed Dementia Rating Scale (BDR) and Clinical Neurological D eficit Rating (CNDR) were used to assess the patients’ intelligence state befor e and after acupuncture treatment. Results: After acupuncture tr eatment, the VD patients’ intelligence in all the five groups was improved at different degrees . Additional acupuncture of each of GV 20, GV 26 and HT 7 had a remarkable e ffec t in improving the VD patients’ fluid intelligence, and could obviously promote their abilities of temporal orientation, spatial orientation and figure drawing ; and additional joint acupuncture of the three acupoints could improve their co gnitive and non-cognitive functions, such as reducing the severity of dementia , raising the temporal orientation, spatial orientation, calculation, short-term m emory and figure drawing abilities, and improving their activities of daily livi ng and personality. Besides, acupuncture of GV 20 could improve the abilities of calculation and short term memory, and correct the personality change of VD pat ients, while acupuncture of GV 26 could improve the abilities of naming and sh or t-term memory. Conclusion: Acupuncture of GV 20, GV 26 and HT 7 all had a certai n therapeutic effect in improving VD; the therapeutic effects of acupuncture of GV 20 and GV 26 were better than that of acupuncture of HT 7; and the effica cy of the three points used in combination was the best.

Autophagy activation aggravates neuronal injury in the hippocampus of vascular dementia rats

It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuro- nal injury in a rat model of vascular dementia. In model rats, hippocampal CA1 neurons were severely damaged, and expression of the autophagy-related proteins beclin-1, cathepsin B and microtubule-associated protein 1 light chain 3 was elevated compared with that in sham-operated animals. These responses were suppressed in animals that received a single intraperitoneal injection of wortmannin, an autophagy inhibitor, prior to model establishment. The present results confirm that autophagy and autophagy-related proteins are involved in the pathological changes of vascular dementia, and that inhibition of autophagy has neuroprotective effects.

Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.

Puerarin decreases hypoxia inducible factor-1 alpha in the hippocampus of vascular dementia rats

In this study, a rat vascular dementia model was established by permanent bilateral common carotid arterial occlusion. Rats were intraperitoneally injected with puerarin 3 days before modeling, for 45 successive days. Results demonstrated that in treated animals hippocampal structures were clear, nerve cells arranged neatly, and cytoplasm was rich in Nissl bodies. The number of cells positive for hypoxia inducible factor-1 alpha, erythropoietin and endothelial nitric oxide synthase was reduced; and the learning and memory abilities of rats were significantly improved. Our experimental findings indicate that puerarin can significantly improve learning and memory in a vascular dementia model, and that the underlying mechanism may be associated with the regulation of the expression of hypoxia inducible factor-1 alpha.

Kongsheng Zhenzhong pill's effect on the learning and memory ability and its neuroprotective effects in vascular dementia rats

Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.

INFLUENCE OF ELECTROACUPUNCTURE ON HYPERTENSION VASCULAR DEMENTIA AND ITS RED CELL IMMUNE FUNCTION IN THE RAT

Objective: To probe into the effect of electroacupuncture (EA)on vascular dementia and red cell immune function in the rat. Methods: 30 SD rats were made into renal hypertension rats(RHR) by clamping the kidney arteries with silver clip. 42 days later, their bilateral common carotid arteries were blocked repeatedly to cause cerebral ischemia. The Hypertension vascular dementia model was then set up. Then they were randomly divided into VD model group, EA groupand medication group (Dihydroergotoxine, DHET), with 10 cases in each group. The therapeutic course was 28 days. The ability of learning and memory was using an obs erved by water maze, and the function of red blood cell immune was detected after treatment. Results: the latecy of the EA group and medication group was shorter than that of model group (P<0.05, P<0.005), and that of EA group was shorter than medication group (P<0.05, P<0.005). EA and medication could increase the RBCC 3b receptor flower circle rate and reduce the RBCIC flower circle rate significantly(P<0.05, P< 0.01). Conclusion: The results indicated that EA therapy could raise the ability of learning and memory and improve the function of red cell immune in VD rats, while the therapeutic effect of EAis better than DHET.

Effects of glossy privet fruit on neural cell apoptosis in the cortical parietal lobe and hippocampal CA1 region of vascular dementia rats

BACKGROUND： Glossy privet fruit inhibits neural cell apoptosis following the onset of vascular dementia. OBJECTIVE： To confirm glossy privet fruit effects on neural cell apoptosis in the cortical parietal lobe and hippocampal CAI region of rat models of vascular dementia using molecular biology techniques. DESIGN, TIME AND SETTING： The neural cell morphology experiment was performed at the Laboratory of Flow Cells and Biochemistry, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, and the Basic Room of Pathology, Academy of Chinese Medicine from December 2006 to May 2008. MATERIALS： A total of 60 Wistar rats were used to establish vascular dementia models using a photochemical reaction method. Glossy privet fruit was purchased from Fujian, China. Hydergine was co-produced by Sandoz, Switzerland and Huajin, China. METHODS： The 60 Wistar rats were randomly divided into 6 equal sized groups （n = 10）, i.e. model, blank, high, moderate and low doses of Chinese medicine, and hydergine control groups. Rats in the model group were treated with distilled water （1 mL/100 g） by gavage following model establishment. Rats in the blank group underwent experimental procedures as for the model group, except that rat models were created without illumination. Rats in the high, moderate and low doses of Chinese medicine groups, and the hydergine control group respectively received high, moderate and low doses of glossy privet fruit, and hydergine suspension （1 mL/100 g） by gavage, once a day, for 30 days. MAIN OUTCOME MEASURES： Morphology of neural cells from the rat cortical parietal lobe and hippocampal CA1 region of all groups was observed with an electron microscope. Positive neural cells in the injury site of the rat cortical parietal lobe and hippocampal CA1 region were investigated using the Fas immunohistochemieal method. Absorbance of Fas-positive neurons was detected by the MPIAS-500 multimedia color imaging analysis system. RESULTS： Neural cells were normal, and nuclei were regular in the right cortical parietal lobe and hippoeampal CA1 region in the blank group. Karyopyknosis, an integral nuclear membrane, vacuole and apoptotic bodies were presented in the model group. The quantity and morphology of neural cells were normal in all doses of Chinese medicine groups, and the hydergine control group. Compared with the model group, absorbance was reduced at the injury site of rat cortical parietal lobe and hippocampal CA1 region in the blank, high, moderate and low doses of Chinese medicine, and hydergine control groups （P 〈 0.05）. The decrease was particularly significant in the blank group （P 〈 0.01 ）, followed by the high dose of Chinese medicine group （P 〈 0.01）. Compared with the model group, the percentage of apoptosis was decreased at the injury site of the rat cortical parietal lobe and hippocampal CAI region in the blank, high, moderate and low doses of Chinese medicine, and hydergine control groups （P 〈 0.01） and this decrease was significant in the high dose of Chinese medicine group （P 〈 0.01）. CONCLUSION： Glossy privet fruit, a kidney-tonifying Chinese herbal medicine, can inhibit cell apoptosis by reducing apoptotic signals induced by cerebral ischemia/hypoxia.

Logistic regression analysis on risk factors for vascular dementia following cerebral infarction in 403 patients from Chongqing City Hospital and family follow-up studies

BACKGROUND： Studies have demonstrated that the risk factors of vascular dementia following stroke are greatly different in region, race and other aspects. OBJECTIVE： To analyze the conditions and incidental risk factors of vascular dementia in patients with acute cerebral infarction from Chongqing City. DESIGN： Case analysis. SETTING： Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA. PARTICIPANTS： Altogether 546 inpatients with acute ischemic stroke admitted to Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA between May 1999 and December 2002 were involved in this study. The involved patients, including 295 males and 251 females, aged 55 - 94 years, dwelled in Chongqing over 5 years. They were admitted to hospital within 48 hours of attack of acute ischemic stroke, and survived for over 3 months. Informed consents were obtained from all the involved subjects. METHODS： ① Following the same standard, cognitive and social function evaluations were conducted by one physician on admission and 3 months after admission, Unified questionnaire, consisting of general characteristics, vascular risk factors, stroke characteristics, neurological physical sign, and other 28 factors of involved subjects, was used in all the patients. According to the investigation results, the patients were assigned into 2 groups： dementia group and non-dementia group. ②Ischemic stroke was diagnosed according to acute ischemic brain disorder 〉 24 hours and CT or MRI imageology.③ Neurophysiological examination was conducted in all the patients at 7 to l0 days after stroke （score was two SD less than or equaled to normal level was considered as abnormal）. ④Diagnosis and statistics of dementia were carried out with Mini-Mental State Examination and The Diagnostic and Statistical Manual of Mental Disorders-Ⅳ （published by American Psychiatric Association） on admission and 3 months after admission. Neurologic deficit scoring was carried out with the National Institutes of Health Stroke Scale. ⑤ Chi-square test was used for categorical variable, and t test for quantitative variable between dementia group and non-dementia group. Dementia-related factors were performed multiple-factor Logistic regression model analysis. MAIN OUTCOME MEASURES： Incidence of dementia and dementia-related risk factors of patients. RESULTS： Altogether 546 patients with stroke were involved in this study, 403 of them participated in the final analysis, and 143 dropped out. A total of 342 were followed-up in the hospital and 61 at home. At 3 months after cerebral infarction, vascular dementia occurred in 87 （21.6%） of 403 patients. The main risk factors were age （OR 1.179; 95%CI 1.130 - 1.230）, low education level （OR 1.806; 95%CI 1.024 - 3.186）, daily alcohol drinking （OR 3.447; 95%（1/ 1.591 - 7.468）, stroke history （OR 2.531; 95%CI 1.419 - 4.512）, atrial fibrilation（OR 3.475; 95%CI 1.712 - 7.057）, dysphonia （OR 5.873; 95%6/2.620 - 13.163） and left carotid artery infarction （OR 1.975; 95%（1/1.152 - 3.388）. CONCLUSION： The incidence of vascular dementia is determined by synthetic action of multiple risk factors. Dysphonia is the most important influencing factor.

Effects of electro-acupuncture on Noxa and caspase-3 expression in hippocampal CA1 region of a vascular dementia rat model

BACKGROUND：Noxa, a pro-apoptotic member of the Bcl-2 protein family, has been shown to induce the mitochondrial pathway of apoptosis and to mediate hypoxic cell death in a rat model of cerebral ischemia. This suggests that Noxa could participate in apoptosis during vascular dementia （VD）. OBJECTIVE： To detect Noxa and caspase-3 expression after electro-acupuncture in VD rats to further validate the mechanism of electro-acupuncture-induced effects in the treatment of VD. DESIGN, TIME AND SETTING： A randomized, controlled study was performed at the Center for the Neurobiology of Fujian Medical University between January 2006 and March 2007. MATERIALS： A total of forty adult, male, Sprague Dawley rats were included in this study. The following equipment was used： confocal laser scanning microscope （Sp5, Leica, Germany）, water maze （Bejing Suntendy Science and Technology Co., Ltd., China）, and SDZ-II electronic acupuncture treatment instruments （Suzhou Medical Appliance Factory, China）. METHODS： Thirty-eight rats with sufficient learning and memory abilities were selected by Morris water maze criteria. Twelve rats received sham-surgery; the remaining 26 rats were used to establish a VD model by bilateral occlusion of the common carotid arteries. The rats that survived the occlusion procedure were randomly assigned into an electro-acupuncture group （n = 11） and a VD model group （n = 12）. MAIN OUTCOME MEASURES： Neuropathological changes were observed with hematoxylin-eosin staining of the hippocampus and expression of Noxa and caspase-3 in the hippocampal CA1 region was analyzed by confocal laser scanning microscope following immunofluorescence staining. RESULTS： Expressions of Noxa and caspase-3 in the electro-acupuncture group and sham-operated group were less than in the VD model group （P 〈 0.01）. Electro-acupuncture reduced the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathways in the electro-acupuncture group compared with the VD model group （P 〈 0.01）. CONCLUSION： Electro-acupuncture can improve learning and memory ability and inhibit the occurrence of apoptosis by blocking expression of Noxa and caspase-3 in the hippocampal CA1 region of VD rats.

Therapeutic effects of dental pulp stem cells on vascular dementia in rat models

Dental pulp stem cells are a type of adult stem cells with strong proliferative ability and multi-differentiation potential. There are no studies on treatment of vascular dementia with dental pulp stem cells. In the present study, rat models of vascular dementia were established by two-vessel occlusion, and 30 days later, rats were injected with 2 × 10^(7) dental pulp stem cells via the tail vein. At 70 days after vascular dementia induction, dental pulp stem cells had migrated to the brain tissue of rat vascular dementia models and differentiated into neuronlike cells. At the same time, doublecortin, neurofilament 200, and Neu N m RNA and protein expression levels in the brain tissue were increased, and glial fibrillary acidic protein m RNA and protein expression levels were decreased. Behavioral testing also revealed that dental pulp stem cell transplantation improved the cognitive function of rat vascular dementia models. These findings suggest that dental pulp stem cell transplantation is effective in treating vascular dementia possibly through a paracrine mechanism. The study was approved by the Animal Ethics Committee of Harbin Medical University(approval No. KY2017-132) in 2017.

Expression of cyclin-dependent protein kinase 5 in the hippocampus of vascular dementia mice after cerebral ischemia and reperfusion

BACKGROUND： The p25-activated cyclin-dependent protein kinase 5 （Cdk5） may induce neuronal cell death and cause the development of dementia following cerebral ischemia and reperfusion. OBJECTIVE： To observe changes in the expression of Cdk5 and p25 in hippocampal tissue of vascular dementia mice at different time points following cerebral ischemia and reperfusion. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed in the clinical trial center of Hebei Provincial People＇s Hospital between September 2007 and October 2008. MATERIALS： Cdk5 rabbit anti-mouse polyclonal antibody, p35 rabbit anti-mouse polyclonal antibody, and β-actin mouse monoclonal antibody were purchased from Santa Cruz Biotechnology, Inc., USA; horseradish peroxidase-labeled goat anti-rabbit IgG and horseradish peroxidase-labeled goat anti-mice IgG were offered by Beijing Zhongshan Geldenbridye Biotechnology Co.,Ltd., China; the protein quantitative kit was produced by Applygen Gene Technology Corp., Beijing, China; cDNA reverse transcription and PCR amplification reagents were products of TianGen＆ Biotech （Beijing） Co.,Ltd., China. METHODS： One hundred and sixty male Kunming mice were randomly divided into two groups： a sham-operated group （n = 65） and a model group （n = 95）. Vascular dementia was induced with three periods of transient ischemia and reperfusion of the bilateral common carotid arteries. In the sham-operated group, the bilateral common carotid arteries were not blocked. MAIN OUTCOME MEASURES： Behavioral tests were done at four and six weeks post surgery. Pathological changes in the hippocampal CA1 region were observed with hematoxylin-eosin staining Cdk5 mRNA expression was examined by RT-PCR, and Western blots were used to evaluate Cdk5 and p25 expression. Learning and memory performance were assayed using the Morris water maze. RESULTS： Vascular dementia reduced learning and memory performance at 4 and 6 weeks post surgery. Vascular dementia also caused severe, time-dependent neuronal damage and death in the hippocampal CA1 region. Dementia induction also increased mRNA and protein expression of Cdk5 and p25 at both 4 and 6 weeks after surgery. CONCLUSION： Cdk5/p25 is involved in the development of vascular dementia in mice following cerebral ischemia and reperfusion.