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.

Pathogenesis, Rehabilitation Assessment, Treatment Status, and Research Progress of Vascular Dementia

Given the global trends in population aging,the prevalence of vascular dementia(VD)is increasing year by year.VD has become the second most common type of dementia and can seriously threaten the quality of life of patients.Since VD is preventable,it is important to study VD clinically in order to improve the prognosis of patients.In recent years,a large number of studies have been carried out at home and abroad,focusing on the pathogenesis,rehabilitation assessment,and treatment of VD.This article is a concise overview of these studies.

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.

A meta-analysis of Chinese herbal medicines for vascular dementia

OBJECTIVE： To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. DATA RETRIEVAL： We retrieved publications from Cochrane Library （2004 to July 2011）, PubMed （1966 to July 2011）, the Chinese Science and Technique Journals Database （1977 to July 2011）, the China National Knowledge Infrastructure （1979 to July 2011）, Google Scholar （July 2011）, and the Chinese Biomedical Database （1977 to July 2011） using the key words ＂Chinese medicine OR Chinese herbal medicine＂ and ＂vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia＂. SELECTION CRITERIA： Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et I＇Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers＇ Handbook 5.0. MAIN OUTCOME MEASURES： Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. RESULTS： We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants （1 605 patients took Chinese medicine decoctions （treatment group）; 1 263 patients took western medicine or placebo）. The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention （relative risk （RR） = 1.27; 95% confidence interval （C/）： 1.18-1.38, P 〈 0.01）. Mini-Mental State Examination scores were higher in patients taking Chinese herbal medicines than in those in the control group （weighted mean difference （WMD） = 2.83; 95%CI： 2.55-3.12, P 〈 0.01）. Patients in the treatment group showed better disease amelioration than those in the control group （Hasegawa Dementia Scale scores; WMD = 2.41, 95%CI： 1.48-3.34, P 〈 0.01）. There were also considerably fewer adverse reactions among those in the treatment group compared with those in the control group （RR = 0.20, 95%CI： 0.08-0.47, P 〈 0.01）. CONCLUSION： Chinese herbal medicine appears to be safer and more effective than control measures in the treatment of vascular dementia. However, the included trials were generally low in quality. More well-designed, high-quality trials are needed to provide better evidence for the assessment of the efficacy and safety of Chinese medicines for vascular dementia.

Arterial hypertension,cerebrovascular diseases and dementia

Arterial hypertension(AH)is the most relevant risk factor for acute cerebrovascular disease in general.However,the prevalence of AH is not the same for the different stroke subtypes and is particularly high in lacunar infarcts and atherothrombotic stroke,low in infarcts of unusual cause and undetermined origin,and intermediate in cardioembolic stroke.This risk factor has also been related to vascular dementia and Alzheimer’s disease and their pathological manifestations(senile plaques,neurofibrillary tangles,hippocampal atrophy).The mechanisms linking AH to Alzheimer’s disease remain to be elucidated but some recent studies showed that white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association.Hypertension-associated pathological changes in the brain and its vasculature include vascular remodelling and impaired cerebral autoregulation like hypoperfusion,ischemia and hypoxia,which may initiate the pathological process of Alzheimer’s disease and the expression of dementia.Therefore,prompt diagnosis and adequate control of hypertension and different vascular risk factors are the rational basis for a more effective strategy in the secondary prevention of cerebrovascular disease and dementia.

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.

Effects of repetitive transcranial magnetic stimulation on cognitive function and cholinergic activity in the rat hippocampus after vascular dementia

Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

Effect of glycosides of Cistanche on the expression of mitochondrial precursor protein and keratin type Ⅱ cytoskeletal 6A in a rat model of vascular dementia

Glycosides of Cistanche（GC）is a preparation used extensively for its neuroprotective effect against neurological diseases,but its mechanisms of action remains incompletely understood.Here,we established a bilateral common carotid artery occlusion model of vascular dementia in rats and injected the model rats with a suspension of GC（10 mg/kg/day,intraperitoneally）for 14 consecutive days.Immunohistochemistry showed that GC significantly reduced p-tau and amyloid beta（Aβ）immunoreactivity in the hippocampus of the model rats.Proteomic analysis demonstrated upregulation of mitochondrial precursor protein and downregulation of keratin type II cytoskeletal6A after GC treatment compared with model rats that had received saline.Western blot assay confirmed these findings.Our results suggest that the neuroprotective effect of GC in vascular dementia occurs via the promotion of neuronal cytoskeleton regeneration.

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.

Improving cognitive impairment by Tongxinluo via inhibiting expression of beta-secretase 1/beta-amyloid peptide in experimental vascular dementia

BACKGROUND： Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid peptide （A β ） in hippocampus？ OBJECTIVE： To observe the effect of Tongxinluo on cognitive impairment in a mouse model with vascular dementia and the changes of A β deposition and β -secretase 1 （BACE1） expression. DESIGN： Randomized controlled study. SETTING： State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School. MATERIALS： The experiment was carried out in the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2006 to January 2007. A total of 36 healthy Kunming mice, 18 of each gender, were chosen. The study was conducted in accordance with the National Regulations of Experimental Animal Administration, and all animal experiments were approved by the Committee of Experimental Animal Administration of Nanjing University. Tongxinluo was provided by Shijiazhuang Yiling Pharmaceutical Co., Ltd. METHODS： All mice were randomly divided into 6 groups, including naive control （n=6）, sham-operated control （n=6） and experimental groups treated with different doses of Tongxinluo （0.2, 0.4, and 0.6 g/kg/d; n=6 for each group） or vehicle （n=6）. Five groups were subjected to bilateral common carotid arteries （2-VO） occlusion to produce a vascular dementia model （no occlusion was performed in sham-operated group）. The mice in the Tongxinluo treatment groups were intragastricly administered daily with a Tongxinluo suspension （40 g/L in distilled water） at doses of 0.2, 0.4 or 0.6 g/kg/d from day 1 to day 30 post-surgery. The animals in vehicle, sham-operated and naive groups were administered an equal volume of distilled water. MAIN OUTCOME MEASURES： ①Escape latency time determined in all groups of mice before and after 2-VO occlusion by Morris water maze. ②Changes in BACEI mRNA expression in the hippocampi of mice among the six groups by RT-PCR assay, and BACEI and A β protein expression in the hippocampi of mice by Western blot. RESULTS： All 36 mice were involved in the final analysis.① No difference was detected in escape latency time to a hidden platform among all groups in water maze test before surgery （P 〉 0.05） At 30 days after 2-VO occlusion, the vehicle animals exhibited a significantly longer latency in finding the hidden platform compared to that of sham-operated and naive animals （P 〈 0.01）. The prolonged escape latency was significantly reduced by oral administration of 0.4 g or 0.6 kg/day （P 〈 0.01, P 〈 0.05）. BACEI mRNA and protein expression in vehicle animals were much higher than in sham-operated and naive animals （P 〈 0.01）. The ischemia-induced increases in BACE1 mRNA and protein level were attenuated by all three doses of Tongxinluo treatment （P 〈 0.01）, and the 0.4 g/kg/d treatment was the most effective. A β protein expression in vehicle animals after 2-VO occlusion were much higher than in sham-operated and naive animals （P 〈 0.01）. 2-VO occlusion-induced A β generation was significantly attenuated by all doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d （P 〈 0.01）. CONCLUSION： BACE1 mRNA levels and protein levels of BACEI and A β are reduced in the hippocampi of vascular dementia model mice by all three doses of Tongxinluo treatment, with the most effective dose being 0.4 g/kg/d. The results suggest that inhibition of post-ischemia BACEI expression and A β generation in brain might underlie Tongxinluo＇s effects in improving cognitive impairment.

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.

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.

Clinical effects of acupuncture therapy for vascular dementia

OBJECTIVE： To evaluate clinical acupuncture treatment studies for vascular dementia, as well as to collect high-quality evidence related to clinical acupuncture treatment for clinical diagnosis. DATA SOURCES： PubMed database （1966-2010）, Embase database （1986-2010）, Cochrane Library （Issue 1,2010）, Chinese Biomedical Literature Database （1979-2010）, China HowNet database （1979-2010）, VlP Journals Database （1989-2010）, and Wanfang database （1998-2010） were analyzed by computer.

Effects of electroacupuncture on the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of rats with vascular dementia

This study investigated the mechanism underlying electroacupuncture therapy for vascular dementia through electroacupuncture at the acupoints of Baihui （DU20）, Dazhui （DU14）, and bilateral Shenshu （BL23） in a rat model of vascular dementia produced by bilateral middle cerebral artery occlusion. Morris water maze test showed that electroacupuncture improved the learning ability of vascular dementia rats. Western blot assay revealed that the expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in vascular dementia rats was significantly increased after electroacupuncture, compared with the model group that was not treated with acupuncture. The average escape latency was also shortened after electroacupuncture, and escape strategies in the spatial probe test improved from edge and random searches, to linear and trending swim pathways. The experimental findings indicate that electroacupuncture improves learning and memory ability by up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein S6 in the hippocampus of vascular dementia rats.

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.