OBJECTIVE: To observe the effect of Huayu Tongluo moxibustion on the NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid protease-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway in rats with vascular dementia (VD), and to explore its mechanism in improving learning and memory ability and alleviating neuronal injury in the hippocampal CA1 region. METHODS: A total of 80 SPF-grade male Wistar rats were included. Three rats were excluded based on the Morris water maze test. From the remaining rats, 12 were randomly selected as the sham operation group. The rest were used to establish VD models via modified bilateral common carotid artery ligation. Thirty-six successfully modeled rats were randomly divided into a model group, a medication group, and a moxibustion group, with 12 rats in each group. The medication group was treated with nimodipine solution (12 mg/kg) via gavage. The moxibustion group was treated with Huayu Tongluo moxibustion. The suspended moxibustion was applied at Shenting (GV24) and Dazhui (GV14), and aconite cake-separated moxibustion was applied at Baihui (GV20), with each acupoint treated for 20 min. All treatments were administered once daily for 21 consecutive days. Before and after modeling, and after intervention, the Morris water maze test was used to assess cognitive function. After intervention, the activation and morphology of microglia in the hippocampal CA1 region were observed by immunofluorescence. Ultrastructure of hippocampal CA1 neurons was examined by transmission electron microscopy. Western blot was used to detect protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, GSDMD, and interleukin-1β (IL-1β) in the hippocampal CA1 region. ELISA was used to detect the content of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) in the hippocampal CA1 region. RESULTS: Compared with the sham operation group, the model group showed longer mean escape latency (P<0.01) and fewer platform crossings (P<0.01); the microglial processes in the hippocampal CA1 region were thickened, cytoplasm was hypertrophic, and relative fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA-1) was increased (P<0.05); the neuronal ultrastructure in the CA1 region was severely damaged, rough endoplasmic reticulum was swollen, mitochondria were deformed and swollen, some cristae were ruptured or dissolved, showing vacuolar changes; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α were significantly elevated (P<0.001). Compared with the model group, both the medication group and the moxibustion group showed shortened mean escape latency (P<0.01) and increased platform crossings (P<0.01); the microglial processes were thinner, and IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was partially improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, and levels of IL-6, IL-8, and TNF-α were significantly reduced (P<0.001). Compared with the medication group, the moxibustion group showed shortened mean escape latency (P<0.05) and more platform crossings (P<0.05); the IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α, were significantly lower (P<0.001). CONCLUSION The Huayu Tongluo moxibustion could enhance learning and memory abilities in VD rats, inhibit excessive activation of microglia, and alleviate neuronal injury in the hippocampal CA1 region. Its mechanism may involve modulation of the NLRP3/Caspase-1/GSDMD signaling pathway, reduction of inflammatory responses.
Animals ; Male ; Dementia, Vascular/physiopathology* ; Rats ; Signal Transduction ; Moxibustion ; Rats, Wistar ; CA1 Region, Hippocampal/injuries* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Caspase 1/genetics* ; Memory ; Humans ; Neurons/metabolism* ; Learning

OBJECTIVETo observe the effect of puerarin on methyl-CpG binding protein 2 (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular dementia (VD).

METHODSThirty-six healthy Sprague-Dawley rats were randomly assigned to the sham-operated group, dementia group and puerarintreated group using a random number table (n=12 per group). The modifified permanent bilateral common carotid artery occlusion method was used to establish the VD model. The sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin-treated group was given 100 mg/(kg•d) of puerarin for 17 days. The learning and memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin staining, immunohistochemical (IHC) staining and Western blot analysis were carried out to observe changes in neuron morphology and in level of pMeCP2 in the hippocampus, respectively.

RESULTSThe morphologies of rat hippocampal neurons in the puerarintreated group were markedly improved compared with the dementia group. The escape latency of the dementia group was significantly longer than the sham-operated group (P<0.05), while the puerarin-treated group was obviously shorter than the dementia group (P<0.05). Cross-platform times of the dementia group were signifificantly decreased compared with the sham-operated group (P<0.05), while the puerarin-treated group was obviously increased compared with the dementia group (P<0.05). IHC staining showed no significant difference in the number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2 positive cells in the CA1 region of hippocampus in the dementia group was signifificantly increased compared with the sham-operated group, and the puerarin-treated group was signifificantly increased compared with the dementia group (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2 expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia group was signifificantly increased compared with the sham-operated group, while it in the puerarin-treated group was signifificantly increased compared with the dementia group (P<0.05).

CONCLUSIONPuerarin could play a role in the protection of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron morphologies, and enhancing learning and memory ablities in a rat model of VD.

Animals ; Dementia, Vascular ; drug therapy ; genetics ; physiopathology ; Hippocampus ; pathology ; Isoflavones ; chemistry ; pharmacology ; therapeutic use ; Memory ; drug effects ; Methyl-CpG-Binding Protein 2 ; metabolism ; Phosphorylation ; drug effects ; Rats, Sprague-Dawley ; Up-Regulation ; drug effects

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

OBJECTIVETo determine the effects of Jiji decoction (Traditional Chinese Medicine) on the cognitive function and oxidative stress in mice with vascular dementia (VD) induced by cerebral ischemia/reperfusion.

METHODSThirty-two mice were randomly divided into nonnal group (n = 8), sham group (operation, but no cerebral ischemia/reperfusi6n, n = 8), model group (vascular dementia model induced by cerebral ischemia/reperfusion, n = 8), and Jiji decoction-treated group (vascular dementia model plus treatment with Jiji decoction, n = 8). Fourteen days of treatment after operation, the cognitive behavior was measured in step-through test, spatial probe test and platform test. Afterwards, to assess the levels of oxidative stress, the activity of superoxide dismutase(SOD) and content of malonaldehyde (MDA) in brain of these mice were measured.

RESULTSData from step-through test indicated that the escaping latency of Jiji decoction-treated group was prolonged and the error counts were decreased significantly ( P <0.01) compared with those of model group. Data from spatial probe test indicated that the time of entering darkroom, the time of climbing height and the time of entering bright room in Jiji decoction-treated group were shortened and the counts of climbing height were increased (P < 0.05-0.01) significantly compared with those of model group. Data from platform test showed that the escaping latency of Jiji decoction-treated group was prolonged significantly (P < 0.01) compared with that of model group. Compared with normal and sham group, the activity of SOD was decreased and the content of MDA was increased in model group significantly (P < 0.01). Compared with those of model group, the levels of SOD and MDA in Jiji decoction-treated group were improved significantly (P < 0.01).

CONCLUSIONJiji decoction could improve cognitive function of VD mice. Its mechanism might be related with the inhibition of oxidative stiess in the brain.

Animals ; Brain ; drug effects ; metabolism ; Cerebral Infarction ; physiopathology ; Cognition ; drug effects ; Dementia, Vascular ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Malondialdehyde ; metabolism ; Medicine, Chinese Traditional ; Mice ; Oxidative Stress ; drug effects ; Reperfusion Injury ; drug therapy ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the effects of acupuncture on Chinese medicine syndromes of vascular dementia (VaD).

METHODSSixty-three VaD patients were divided into three groups. Those willing to be randomized were randomly assigned to receive either acupuncture (random acupuncture group, 24 cases) or rehabilitation training (guided rehabilitation group, 24 cases) for 6 weeks. Those unwilling to be randomized also received acupuncture for 6 weeks (non-random acupuncture group, 19 cases). Patient syndromes and their severity were evaluated before treatment (baseline), at the end of treatment, and at 4-week follow-up after the completion of treatment using a CM scoring system (scale of differentiation of syndromes of vascular dementia, SDSVD). The SDSVD scores of the random and non-random acupuncture groups, and of all patients who received acupuncture (combined acupuncture group, 43 cases), were compared with those in the guided rehabilitation group.

RESULTSIn the random, non-random, and combined acupuncture groups, SDSVD scores were significantly reduced at the end of treatment and at follow-up than at baseline. In the guided rehabilitation group, SDSVD scores were similar to baseline scores at the end of treatment and at follow-up. However, there were no significant differences in SDSVD scores among the three groups or between the combined acupuncture group and the guided rehabilitation group at any time points. In the non-random and combined acupuncture groups, SDSVD scores were significantly reduced at the end of treatment than at baseline in patients with hyperactivity of Liver (Gan)-yang or phlegm obstruction of the orifices.

CONCLUSIONSAcupuncture reduced the severity of VaD. The improvement was the greatest in patients undergoing their treatment of choice. Treatments in this study were more effective for excess syndromes, such as Liver-yang hyperactivity or phlegm obstruction of the orifices than deficiency syndromes, such as Kidney (Shen)-essence deficiency.

Acupuncture ; Dementia, Vascular ; physiopathology ; therapy ; Humans ; Medicine, Chinese Traditional

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

This study is to investigate the effect of ferulic acid on learning and memory impairments of vascular dementia (VD) rats and its mechanism of action. VD rats model was replicated by permanent bilateral common carotid artery occlusion (2VO). The learning and memory capability of VD rats was evaluated by Morris water maze. The activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD) and the content of glutamic acid (Glu) and malondialdehyde (MDA) in hippocampus of VD rats' brain were determined, separately. The results showed that ferulic acid could alleviate learning and memory deficits of VD rats significantly. Ferulic acid was found to inhibit the activity of AChE and increased the activity of SOD in rat hippocampus. In addition, ferulic acid could also decrease the content of Glu and MDA in rat hippocampus. These results suggested that ferulic acid could alleviate VD rats' learning and memory deficits, which might be due to antioxidation, the improvement of cholinergic system in brain, or the inhibitory of nerve injury by excitatory amino acids.
Acetylcholinesterase ; metabolism ; Animals ; Anticoagulants ; pharmacology ; therapeutic use ; Coumaric Acids ; pharmacology ; therapeutic use ; Dementia, Vascular ; metabolism ; physiopathology ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Memory Disorders ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

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

OBJECTIVETo investigate the sleep structure in patients with vascular cognitive impairment-no dementia (VCI-ND) and its differences from that of normal individuals.

METHODSThe whole night sleep record of 20 patients with VCI-ND were monitored by 32-head video-taped polysomnographic system, and the results were compared with the data of 20 normal subjects.

RESULTSCompared with normal subjects, patients with VCI-ND showed significantly reduced total sleep duration, increased waking times, increased stage 1 sleep, decreased stage 2 sleep, decreased stage 3 sleep, decreased rapid eye movement stage (REM) and reduced sleep efficiency.

CONCLUSIONIncreased light sleep as well as decreased slow-wave stage 3-4 sleep and decreased REM stage may be a specific electroneurophysiologic marker for VCI-ND, but large-sampled multi-centered randomized controlled trial is necessary to test the validity of these features as specific markers for screening and early diagnostic purposes.

Aged ; Case-Control Studies ; Cognition Disorders ; diagnosis ; etiology ; physiopathology ; Dementia, Vascular ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Polysomnography ; Sleep ; physiology ; Sleep Stages ; Sleep Wake Disorders ; etiology ; Stroke ; complications

OBJECTIVETo observe the effect of Shengmaisan on the learning and memory abilities and the expression of nitric oxide synthase and neuron apoptosis in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of Shengmaisan for treatment of VD.

METHODSWistar rats were divided randomly in to normal control group, sham-operated group, VD model group, high-dose Shengmaisan group, low-dose Shengmaisan group, and nimodipine group. In the latter 4 groups, bilateral common carotid artery occlusion (BCCAO) was performed to establish rat models of VD followed by intragastric administration of Shengmaisan at 10 or 30 g.kg(-1).day(-1) or nimodipine at 20 g.kg(-1).day(-1) accordingly. The rats in the control, sham-operated and model groups were given saline in the same manner. The improvement of learning and memory abilities of the rats was assessed using Morris water maze test, and NOS activity and neuronal apoptosis in the hippocampus were determined after the treatment.

RESULTSThe learning and memory ability and hippocampal NOS activity and neuronal apoptosis in low-dose Shengmaisan group and nimodipine group were significantly different from those in the VD model group (P<0.01), but no significant differences were found between high-dose Shengmaisan group and nimodipine group (P>0.05).

CONCLUSIONShengmaisan can significantly improve the learning and memory abilities of VD rats but may not be able to totally reverse the damage. The therapeutic effect of Shengmaisan might be related to its effect in decreasing NOS activity and inhibiting neuronal apoptosis in the hippocampus.

Animals ; Apoptosis ; drug effects ; Dementia, Vascular ; drug therapy ; pathology ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hippocampus ; metabolism ; pathology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Neurons ; pathology ; Nitric Oxide Synthase ; metabolism ; Phytotherapy ; Random Allocation ; Rats ; Rats, Wistar