This study aims to explore the effects and potential mechanisms of Modified Shuyu Pills in ameliorating depressive behaviors in the mouse model of vascular dementia(VaD). Seventy-two three-month-old male C57BL/6 mice were assigned into six groups: sham, model, low-, medium-, and high-dose Modified Shuyu Pills, and fluoxetine. The other five groups except the sham group underwent bilateral common carotid artery stenosis combined with chronic unpredictable stress. Depressive behaviors were assessed by the sucrose preference test and tail suspension test. Cerebral blood flow was measured by laser speckle imaging. Protein levels of low density lipoprotein receptor(LDLR), mitogen-activated protein kinase kinase(MEK), phosphorylated(p)-MEK, extracellular signal-regulated kinase(ERK), and p-ERK in the ventral tegmental area(VTA) and nucleus accumbens(NAc) were determined by Western blot. The fluorescence intensity of myelin basic protein(MBP) in the VTA and NAc were measured by immunofluorescence. Myelin sheath morphology in the VTA and NAc was observed by luxol fast blue staining, and the ultrastructure of myelin sheath in the VTA and NAc was examined by transmission electron microscopy. In the tail suspension test, the immobility time of the model group was longer than that of the sham group(P<0.01). In the sucrose preference test, the sucrose preference rate of the model group was lower than that of the sham group(P<0.01). After intervention with Modified Shuyu Pills, the immobility time in the tail suspension test was shortened(P<0.01), and the sucrose preference rate increased(P<0.01). Laser speckle imaging results showed that compared with the sham group, the model group showed reduced cerebral blood flow(P<0.01), and the reduction was reversed by medium-and high-dose Modified Shuyu Pills(P<0.01). Western blot results indicated that the relative expression levels of LDLR, p-MEK/MEK, and p-ERK/ERK in the VTA and NAc of the model group were lower than those in the sham group(P<0.01). Medium-and high-dose Modified Shuyu Pills reversed this trend(P<0.01). Immunofluorescence results showed that the fluorescence intensity of MBP in the VTA and NAc of the model group was lower than that of the sham group(P<0.01). The medium-and high-dose Modified Shuyu Pills groups showed increased fluorescence intensity of MBP in the VTA compared with the model group(P<0.01). In the NAc, the fluorescence intensity of MBP in all the groups of Modified Shuyu Pills increased to varying degrees compared with that in the model group(P<0.01). Luxol fast blue staining results showed that the model group presented lighter staining intensity and looser arrangement of myelin fibers than the sham group, indicating significant demyelination in the model group. However, after intervention with medium-and high-dose Modified Shuyu Pills, the staining intensity and myelin sheath structure in the VTA and NAc were improved. Transmission electron microscopy results revealed that the myelin sheath in the VTA and NAc of the sham group was intact and dense, while the model group exhibited extensive myelin loss, with myelin sheath degeneration and disintegration. After intervention with Modified Shuyu Pills, the myelin sheath loss in the VTA and NAc of mice was reduced, and the proportion of myelinated tissue increased. In summary, Modified Shuyu Pills may promote myelination via the VTA-NAc circuit by upregulating the LDLR/MEK/ERK signaling pathway, thereby ameliorating depressive-like behaviors in VaD mice.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Ventral Tegmental Area/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Depression/genetics* ; Receptors, LDL/genetics* ; Dementia, Vascular/psychology* ; MAP Kinase Signaling System/drug effects* ; Nucleus Accumbens/metabolism* ; Behavior, Animal/drug effects* ; Humans ; Myelin Sheath/drug effects* ; Extracellular Signal-Regulated MAP Kinases/genetics*

Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test. Moreover, SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats, thereby alleviating VaD. Mechanistically, SYD caused increases in the expression of vascular endothelial growth factor (VEGF), CD34 and CD31, compared with the MCAO rats in coronal hippocampus. Simultaneously, the expression level of miR-210 was elevated significantly after SYD administration, compared with the vehicle rats (P < 0.01). The expression of Notch 4 at both mRNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats (P < 0.05). Overall, the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced miR210 expression to activate Notch pathway, and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats, ultimately enhancing the cognition and memory of MCAO rats. Therefore, our findings preliminarily identified the effect and the mechanism of action for SYD on VaD in rats. SYD could be a potential candidate in treatment of VaD.
Angiogenesis Inducing Agents ; administration & dosage ; Animals ; Dementia, Vascular ; drug therapy ; genetics ; metabolism ; psychology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Memory ; drug effects ; Neuroprotective Agents ; administration & dosage ; Rats ; Rats, Wistar ; Receptor, Notch4 ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

INTRODUCTIONHyperfamiliarity, a phenomenon in which feelings of familiarity are evoked by novel stimuli, is well described in epilepsy and the lesioned brain. Abnormality of familiarity in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have also been described in the literature, but more from a neuropsychological approach perspective. Currently, there is a lack of study on the real-life experience of familiarity abnormality in dementia and MCI. Our aim was to compare the occurrence of hyperfamiliarity among dementia and MCI.

MATERIALS AND METHODSWe recruited 73 participants, 29 with AD, 10 with vascular dementia, 7 with MCI and 27 healthy controls, and administered a questionnaire to assess hyperfamiliarity frequency.

RESULTSHyperfamiliarity was observed in real-life in cognitive impairment, but was unrelated to its severity or underlying aetiology.

CONCLUSIONThis study highlights the similar rate of occurrence of hyperfamiliarity in the daily life of individuals with cognitive impairment. Future research should examine neuropsychological correlations and mechanisms that contribute to such observations.

Aged ; Aged, 80 and over ; Alzheimer Disease ; physiopathology ; psychology ; Case-Control Studies ; Cognitive Dysfunction ; physiopathology ; psychology ; Dementia ; physiopathology ; psychology ; Dementia, Vascular ; physiopathology ; psychology ; Female ; Humans ; Male ; Middle Aged ; Recognition (Psychology) ; Severity of Illness Index ; Singapore

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.
Animals ; Calcium ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Dementia, Vascular ; complications ; drug therapy ; metabolism ; psychology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Hippocampus ; drug effects ; metabolism ; Learning Disabilities ; drug therapy ; etiology ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Memory Disorders ; drug therapy ; etiology ; metabolism ; Phytotherapy ; Rats, Sprague-Dawley ; Signal Transduction ; Up-Regulation

OBJECTIVETo compare the therapeutic differences among scalp acupuncture combined with auricular point sticking, body acupuncture and western medication for treatment of vascular dementia (VD).

METHODSNinety cases were randomly divided into a combined therapy group (31 cases), a body acupuncture group (29 cases) and a western medication group (30 cases). The combined therapy group was treated with scalp acupuncture at forehead middle line, parieral middle line, temporal front line and temporal rear line as well as auricular point sticking at naogan (AT3,41), shen (CO10), shenmen (TF4), zhen (AT3), once a day; the body acupuncture group was treated with acupuncture at Baihui (GV 20), Fengchi (GB 20), Zusanli (ST 36) and so on, once a day; the western medication group was treated with oral administration of aniracetam tablets, 0.2 g per time, twice a day. Fourteen days were considered as a treatment course, and totally 3 courses were required. The mini-mental state examination (MMSE) and activities of daily living (ADL) were applied to assess the changes of cognitive behavior ability before and after treatment among three groups. Also the efficacy among three groups were compared.

RESULTSOne case dropped out in the body acupuncture group and western medication group, respectively. The total effective rate was 90.334 (28/31) in the combined therapy group, which was superior to 85.734 (24/28) in the body acupuncture group and 79.3% (23/29) in the western medication group (both P < 0.05). After the treatment, the scores of MMSE and ADL were all improved among three groups, which was the most significant in the combined therapy group (MMSE: 23.32 +/- 4.45 vs 21.23 +/- 4.13, P < 0.05; 23.32 +/- 4.45 vs 20.41 +/- 4. 01, P < 0.01; ADL: 53.18 +/- 21.55 vs 51.92 +/- 20.42, P < 0.05; 53.18 +/- 21.55 vs 49.42 +/- 19.43, P < 0.01).

CONCLUSIONThe scalp acupuncture combined with auricular point sticking could improve the clinical symptoms and cognitive behavior ability in patients with vascular dementia, which has superior total efficacy to body acupuncture and western medication aniracetam tablets.

Activities of Daily Living ; Acupuncture Points ; Acupuncture Therapy ; Aged ; Cognition ; Dementia, Vascular ; psychology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Scalp

OBJECTIVETo verify the therapeutic effect of vascular dementia treated with three-line puncture on the Governor Vessel and Bladder Meridian on head.

METHODSSixty cases were randomly divided into a head-line puncture group and a routine acupuncture group, 30 cases in each group. In head-line puncture group, line puncture was applied on three lines of the Governor Vessel and Bladder Meridian from anterior hairline to occipital tuberosity. In routine acupuncture group, Yintang (GV 29), Fengchi (GB 20), Sishencong (EX-HN 1) penetrating to Baihui (GV 20) and Shenting (GV 24) penetrating to Shangxing (GV 23) were selected. Once a day, 5 times in a week and 8 weeks totally. Score was evaluated with Mini-Mental State Examination scale (MMSE) before and after treatment, and the therapeutic effects in both groups were compared.

RESULTSThe total effective rate of cognitive function was 76. 7% (23/30) in head-line puncture group, superior to that of 43.3% (13/30, P < 0.05) in routine acupuncture group. The MMSE scores in both groups were improved after treatment (both P < 0.01), and it in head-line puncture group was superior to that in routine acupuncture group (P < 0.01).

CONCLUSIONThree-line acupuncture on the Governor Vessel and Bladder Meridian on head can remarkably improve the cognitive function of vascular dementia, and the therapeutic effect is superior to that of routine acupuncture.

Acupuncture Therapy ; Aged ; Cognition ; Dementia, Vascular ; physiopathology ; psychology ; therapy ; Female ; Head ; physiopathology ; Humans ; Male ; Meridians ; Middle Aged ; Treatment Outcome

OBJECTIVETo explore the diffusion-tensor imaging (DTI) characteristics of normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) on conventional magnetic resonance imaging (MRI) in patients with subcortical ischemic vascular disease (SIVD) and examine the relation of such features with the general cognitive function of the patients.

METHODSDTI was performed in 46 SIVD patients and 34 age-matched control subjects with normal MRI findings. The apprarent diffusion coeeficient (ADC) and fractional anisotropy (FA) were measured within the regions of white matter lesions (WMLs), NAWM and NAGM. All the subjects were examined by neurologists with MMSE and clinical neurologic examination.

RESULTSCompared with normal controls, SIVD subjects showed increased ADC values in the subcortical NAGM and NAWM in anterior periventricular and centrum semiovale, with decreased FA values in the caudate nucleus, thalamus and centrum semiovale. An increased severity of the WMLs was associated with increased ADC and decreased FA in the NAWM of SIVD patients. After controlling for age, the ADC in the NAWM of the posterior periventricular, NAWM and WMLs in the centrum semiovale, caudate nucleus and thalamus showed significant inverse correlations to MMSE; FA values in NAWM of the anterior periventricular and WMLs of the centrum semiovale were positively correlated to MMSE.

CONCLUSIONIn SIVD patients, the NAWM and NAGM regions shown by MRI contain diffusion abnormalities, and these abnormalities shown by DTI are significantly correlated to the general cognitive function of the patients.

Aged ; Anisotropy ; Brain Ischemia ; physiopathology ; psychology ; Case-Control Studies ; Cerebral Cortex ; pathology ; Cognition ; physiology ; Cognition Disorders ; pathology ; physiopathology ; Dementia, Vascular ; pathology ; physiopathology ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Male ; Middle Aged

BACKGROUNDAging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.

METHODSTotally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group, D-gal + 2VO group, D-gal + 2VO + saline water group, and D-gal + 2VO + BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation; moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).

RESULTSTransplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal + 2VO + BMSC group showed significant improvement than the D-gal + 2VO group but was still obviously worse than the control group (both P < 0.05). There was no significant difference in swimming speed for all 5 groups.

CONCLUSIONSD-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.

Aging ; Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; methods ; Carotid Stenosis ; complications ; Cognition Disorders ; surgery ; Dementia, Vascular ; psychology ; surgery ; Disease Models, Animal ; Galactose ; toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Stromal Cells ; cytology ; transplantation

BACKGROUND: Physical disability may result in some impairment of the score for Instrumental Activities of Daily Living (IADL). The aim of this study was to evaluate the effect of physical disability on IADL in patients with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), subcortical vascular dementia (SVD), and vascular mild cognitive impairment of the subcortical type (svMCI). METHODS: Fifty-six patients with AD, 30 with SVD, 27 with aMCI, and 21 with svMCI were recruited consecutively from a memory clinic. Informants for the subjects completed a Korean version of the IADL (K-IADL). In addition, the informants were asked to choose the cause of each dependent activity of K-IADL from the following: cognitive impairment, physical disability, or both. The cause of the physical disability was defined as being focal neurologic symptoms, other physical disease, or both. RESULTS: Compared to AD patients, SVD patients had higher K-IADL scores [2.02+/-0.80 (mean+/-SD) vs. 1.45+/-0.90, p<0.01] and focal neurologic signs (FNS; 8.0+/-5.8 vs. 0.0+/-0.0, p<0.001), and lower Barthel Index scores (14.7+/-5.1 vs. 19.6+/-1.2, p<0.001). Patients with svMCI had higher FNS (3.8+/-4.5 vs. 0.0+/-0.0, p<0.001) compared to those with aMCI. The most common cause of dependency of activities in K-IADL was cognitive impairment in AD, aMCI, and svMCI patients, and the combined effect of cognitive impairment and physical disability in those with SVD. The cause of physical disability was FNS in 96% of SVD patients and in all patients with svMCI. CONCLUSIONS: The effects of FNS as well as cognitive impairment should be considered when measuring the IADL of the patients with SVD or svMCI.
Activities of Daily Living ; Alzheimer Disease ; Dementia, Vascular ; Dependency (Psychology) ; Humans ; Memory ; Mild Cognitive Impairment ; Neurologic Manifestations

OBJECTIVETo search for an effective therapy for vascular dementia (VD).

METHODSOne hundred and twenty cases of VD were randomly divided into 2 groups, 60 cases in each group. The observation group were treated with puncturing with needles in alignment at the hairline region and the control group with oral administration of Duxil. Hasegawa's dementia scale (HDS), mini-mental state examination (MMSE), functional activity questionnaire (FAQ), nerve function defect (NFD) and main symptoms (MS) scales were used for assessment of symptoms and signs before and after treatment.

RESULTSChanges of scores for HDS, MMSE, FAQ, NFD and MS before and after treatment had statistically very significant differences (P < 0.01) in the two groups, with significant difference between the two groups (P < 0.05). The total effective rate was 88.33% in the observation group and 81.67% in the control group with a significant difference between the two groups (P < 0.05).

CONCLUSIONPuncturing with needles in alignment at the hairline region has definite therapeutic effect on vascular dementia.

Acupuncture Therapy ; methods ; Aged ; Dementia, Vascular ; psychology ; therapy ; Female ; Humans ; Male ; Middle Aged