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.

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.

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.

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.

Neuroprotective effects of tetrandrine against vascular dementia

Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S.Moore,and has specific therapeutic effects in ischemic cerebrovascular disease.Its use in vascular dementia has not been studied fully.Here,we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia.Eight weeks after model establishment,rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks.Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials,and spent less time swimming in the target quadrant in probe trials,than sham-operated rats.However,rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats.Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage,and more living cells,in the hippocampus of rats treated with tetrandrine than in untreated model rats.Western blot assay showed that interleukin-1β expression,and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472,were lower in model rats that received tetrandrine than in those that did not.The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression,N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472,and neuronal necrosis.

Dynamic changes of glial fibrillary acidic protein and nestin in the hippocampus of adult rat brain following ischemic vascular dementia

Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days （P 〈 0.01）. The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of 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.

Optogenetic activation of glutamatergic neu⁃rons in somatosensory cortex promotes remy⁃elination in ischemic vascular dementia

OBJECTIVE Chronic cerebral hy⁃poperfusion can lead to progressive demyelin⁃ation and ischemic vascular dementia,yet there are no effective treatments.METHODS Magnetic resonance imaging was employed in patients with white matter damage,and optogenetics and skin stroking were exerted to activate glutamater⁃gic neurons in the somatosensory cortex in a clas⁃sical mouse model of ischemia vascular dementia.RESULTS White matter damage was correlated with disrupted cortical structure from MRI results.In a mouse model,activating glutamatergic neu⁃rons in the somatosensory cortex promotes prolif⁃eration of OPCs and remyelination to rescue cog⁃nitive impairment after chronic cerebral hypoper⁃fusion.Such therapeutic action was limited to stimulation with moderate intensity at the upper layers of the cortex,but was achieved over a wide time window after ischemia.Mechanistically,enhanced glutamatergic neuron-OPC functional synaptic connections are required for protection from activation of cortical glutamatergic neurons.Finally,skin stroking activation of the somatosen⁃sory cortex,an easier approach for clinical trans⁃lation,promoted OPC proliferation and remyelin⁃ation as well as cognitive recovery after cerebral hypoperfusion.CONCLUSION Activation of gluta⁃matergic neurons in the somatosensory cortex may serve as novel approaches for treating isch⁃emic vascular dementia through precise modula⁃tion of glutamatergic neuron-OPC circuits.

Advances in TCM Treatment of Senile Vascular Dementia

Senile vascular dementia refers to organic loss of intellectual function due to cerebral damages caused by insufficient blood supply. The following is a summaryon achievements in its etiology, pathogenic mechanism, type identification and treatment in TCM, and the compound formulas, special formulas and drugs, and thepatent drugs used successfully for its treatment. ……

Combined measurement of thyroid and plasma homocysteic acid for detecting the severity of vascular dementia

BACKGROUND: Recent researches demonstrate that onset of cerebral infarction always accompanies with obvious changes of function of thyroid axis; while, high-homocysteic acidemia has been proved as one of risk factors of vascular dementia and Alzheimer disease. Meanwhile, it is found that level of plasma homocysteic acid is positive correlation with injured degrees of cognitive function and brain damage. OBJECTIVE: To observe the changes of function of thyroid and level of homocysteic acid among patients with vascular dementia and compare with those patients without dementia cerebral infarction. DESIGN: Randomized grouping and contrast observation. SETTING: Department of Neurology, People’s Hospital Affiliated to Yunyang Medical College, South China Hospital of Wuhan University. PARTICIPANTS: A total of 38 patients with vascular dementia were hospitalized in the Department of Neurology, People’s Hospital Affiliated to Yunyang Medical College from February 2004 to December 2005. All patients met the diagnostic criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) established by American Psychiatric Association. Based on educational degrees, Mini-mental Status Examination (MMSE) was classified into illiteracy (≤ 17 points), education of primary school (educational duration ≤ 6 years, ≤ 24 points) and education of middle school or above (educational duration > 6 years, ≤ 24 points). Forty patients with non-dementia cerebral infarction were regarded as the control group and checked with CT examination. There were no significant differences of sex and age between the two groups. All patients and relatives were provided the consent. METHODS: Within 24 hours after hospitalization, patients with vascular dementia received MMSE scores, and the degrees were classified based on the scoring results: mild (20-24 points), moderate (10-19 points) and severe (below 10 points). Levels of thyroxine were measured with radioimmunodetection and content of homocysteic acid was measured with high performance liquid chromatogram (HPLC) electrochemical detection. MAIN OUTCOME MEASURES: Levels of homocysteic acid and thyroxine among patients with vascular dementia and non-dementia cerebral infarction. RESULTS: A total of 38 patients with vascular dementia and 40 patients with non-dementia cerebral infarction were involved in the final analysis. ① Levels of triiodothyronine (T3), thyroxine (T4) and free T3 (FT3) were (0.9±0.4) μg/L, (92.9±26.4) μg/L and (3.9±1.8) pmol/L in vascular dementia group respectively, which were higher than those in control group [(1.3±0.3) μg/L, (110.2±28.7) μg/L, (7.2±2.1) pmol/L, t =2.766 6-7.433 6, P < 0.01]; while, level of homocysteic acid was (29.57±7.12) μmol/L in vascular dementia group, which was higher than that in control group [(24.53±4.98) μmol/L, t =3.637 7, P < 0.01]. There were no significant differences of free T4 (FT4) and thyrotropic-stimulating hormone (TSH) between the two groups (P > 0.05). ② Levels of FT3 of patients with mild, moderate and severe vascular dementia were (1.0±0.2), (0.9±0.1) and (0.8±0.1) μg/L, respectively; levels of homocysteic acid were (26.52±4.84), (29.59±5.56) and (32.71±6.17) μmol/L, respectively. There were significant differences among patients at the three degrees of vascular dementia (F =3.59-32.4, P < 0.01). However, there were no significant differences of T4, FT4 and TSH among the three kinds of patients (P > 0.05). CONCLUSION: Levels of thyroxine of patients with vascular dementia decrease; however, levels of homocysteic acid increase. Therefore, the results can indirectly reflect severities of vascular dementia.

MRI evaluation of vascular dementia

OBJECTIVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions. DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the of 'MRI, vascular dementia'. Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database. STUDY SELECTION: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched. DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded. DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia. Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia. CONCLUSION: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.

CLINICAL STUDY ON TREATMENT OF VASCULAR DEMENTIA WITH ELECTROACUPUNCTURE OF "SISHENCHONG

Aim: To observe the therapeutic effect of electroacupuncture (EA) in the treatment of vascular dementia. Methods: A total of 46 cases of vascular dementia (VD) patients were divided into 3 classes according to the scores of the revised Hasegawa dementia scale (HDS), and then randomized into EA group (n=23) and medication (Nimodipine) group (n=23). The acupoints used were "Zhisanzhen" [Shenting (GV 24) and bilateral Benshen (GB 13)] and Sishenchong (EX HN 1) etc.. Scores of HDS, ability of daily life (ADL), neurofunctional defect and main symptoms were used as the indexes for assessing the therapeutic effect. Results: Following treatment, scores of HDS and ADL of two groups increased significantly, while those of neurofunctional defect and main symptoms decreased evidently (P<0.01), and the therapeutic effect of EA was obviously superior to that of medication (P<0.01). Conclusion: EA of "Zhisanzhen" and Sishenchong (EX HN 1) is a good approach for treatment of VD.

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.

Recommendation for and comparison of three types of dementia： Alzheimer’s disease, subcortical ischemic vascular dementia, and mixed dementia

With the progress in global demography of aging, dementia has become a great world health-care issue that require urgent attention and settlement. Demen-tia can arise from a variety of factors, such as neuronal degeneration for Alzheimer’s disease （AD）, vascular risk factors and multiple infarcts for vascular dementia （VaD）, and both degeneration and vascular factors for mixed de-mentia （MD）. Pathophysiology of AD includes the amy-loid and tau protein hypothesis, and infammation-related mechanisms are also widespread mentioned. Subcortical ischemic vascular dementia （SIVD）, a subtype of VaD, is commonly caused by complete or incomplete lacunar infarction of VaD pathology. MD involves both degenera-tion and vascular factors, and the interaction between the two results in the complication of the pathological mech-anism and clinical phenotype. The clinical manifestationsof AD are often divided into four stages according to the progress of the disease, while the phenotypes of SIVD usually has two categories. As for MD, the phenotypes are complex and diverse. Several clinical studies showedthat its symptoms and signs are more similar to SIVD than AD. This article aims to analyze and compare the differ-ent aspects of the three kinds of dementia.

Clinical Study on Effect of Yuantong Capsule in Treating Vascular Dementia

Objective: To observe the clinical effect of Yuantong Capsule (YTC) in treating vascular dementia (VD). Methods: Eighty-three patients of VD were randomized on ratio of 2 : 1 into two groups, the 54 patients in the treated group were treated with YTC orally administered, 3 times a

Evaluation of the Clinical Efficacy of Acupuncture and Moxibustion Combined with Repetitive Transcranial Magnetic Stimulation on Cognitive Function and Sleep Disorders in Patients with Mild Vascular Dementia

Objective:To explore the clinical effects of acupuncture and repeated transcranial magnetic stimulation in patients with mild vascular dementia.Method:From May 2020 to May 2021,40 patients with mild vascular dementia in Harbin Fourth Hospital(our hospital)were divided into the experimental group(20 cases,using conventional drugs+acupuncture+repeated transcranial magnetic stimulation)and the control group(20 cases,for example,the application of conventional medication).The improvement of cognitive function score,sleep quality score,quality of life score,and cerebral hemodynamics before and after treatment were compared between the two groups.Result:Before treatment,the difference in cognitive function score,sleep quality score,quality of life score,and cerebral hemodynamic index between the two groups of patients did not form,that is,p>0.05;after treatment,the experimental group5s cognitive function score was(19.45±2.47)points,Sleep quality score(12.18±2.09),quality of life score(33.29±4.08),left cerebral blood flow velocity(65.76±3.32)cm/s,right cerebral blood flow velocity(64.32±3.25)cm/s,more For the control group,P<0.05・Conclusion:In the clinical treatment of patients with mild vascular dementia,based on conventional drugs,combined with acupuncture and repetitive transcranial magnetic stimulation,the patients?cognitive function can be improved,and the quality of sleep and quality of life can be improved.Comprehensive clinical promotion.

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.

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.