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Abstract: Vascular dementia (VaD) is the second most common cause of dementia in the world today. In this paper, we observed the effect of acupuncture on memory impairment, apoptosis and expression of Bcl-2 and Bax in hippocampus of cerebral multi-infarction rats. The results indicated that acupuncture significantly improved memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time in the target quadrant. Meanwhile, based on the observation in hippocampal CA1 region through methods of the terminal deoxynucleotidyl transferase nick end labeling (TUNEL), immunohistochemistry and in situ hybridization, acupuncture decreased the number of apoptotic cells and expression of the proapoptotic Bax gene, on the contrary, it increased expression of the antiapoptotic gene Bcl-2. The result of the research suggested that acupuncture can exert antiapoptotic effect through counter-regulating Bcl-2 and Bax gene expression. [Copyright &y& Elsevier]

Introduction: Despite acupuncture having been successfully used for the clinical treatment for vascular dementia in Asian countries for centuries, scientifically rigorous evidence is lacking for standardizing therapeutic parameters. To address this problem, it is necessary to examine the parameters of acupuncture using scientific methodology. The goal of this study is to investigate various therapeutic parameters, including manipulation, retention, and frequency of acupuncture, and their contribution to the efficacy of acupuncture in VD. Methods: We selected needle retention, treatment frequency, and needle rotation as the parameters. Acupuncture was performed on acupoints ST36 and GV20. Morris Water Maze was selected to assess the effect of acupuncture on cognitive function and Nissl staining indicated the hippocampal neuronal damage in VD rats. Results: Acupuncture stimulation resulted in a significant improvement in the spatial learning and memory deficit and reversed neuronal damage in the hippocampus. The approach of needle retention with 10 min, rotation for 30s every 5 min or daily treatment with acupuncture was more effective than nonretention, nonrotation, or alternative day treatment group. Conclusion: This study demonstrated that needle retention, treatment frequency, and needle manipulation are important factors in improving the learning and memory as well as reducing the neuronal damage of the hippocampus in a rat VD model. These findings strongly suggest that the appropriate therapeutic parameters could significant influence the efficiency in animal experiments. A series of appropriate therapeutic parameters, including rotating, retaining and frequency, could strongly influence the effectiveness of acupuncture in VD. Provide a new treatment plan that manipulation with twisting‐twirling, retaining needle at least 10 min and once a day treatment after 2VO surgery 1 day or 3 days for future experiments of VD rat. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of acupuncture in patients with vascular cognitive impairment no dementia (VCIND) in comparison with citicoline, an agent for cognitive disturbances associated with chronic cerebral disorders. Design: A randomized controlled multicenter trial. Setting: In three hospitals in Beijing, China. Subjects: A total of 216 patients with VCIND were recruited. Interventions: Patients with VCIND (mean age of 65.4 years) were randomized to receive acupuncture (two sessions per week) or oral citicoline (100 mg three times daily) over three months. Main measures: The primary outcome was the change from baseline to three months in cognitive symptom, measured by Alzheimer's disease Assessment Scale, cognitive subscale (ADAS-cog). Secondary outcomes included changes from baseline to six months in ADAS-cog, executive function measured by the Clock Drawing Test (CDT), and functional disability measured by the Ability of Daily Living (ADL) scale at three and six months. Results: At three months, the acupuncture group had a greater decrease in mean ADAS-cog score (−2.33 ± 0.31) than the citicoline group (−1.38 ± 0.34) with a mean difference of −0.95 (95% CI, −1.84 to −0.07, P = 0.035). The mean change from baseline to six months in ADAS-cog also significantly favored acupuncture treatments (acupuncture change −2.61 vs citicoline −1.25, difference: −1.36 points; 95% CI, −2.20 to −0.51; P = 0.002). There was no difference between the two groups on CDT and ADL scores at either time point. Conclusion: Compared with citicoline, acupuncture has comparable and even superior efficacy with improved cognitive and daily living performance as a complementary and alternative medicine treatment for VCIND. [ABSTRACT FROM AUTHOR]

Summary: Aims: Acupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high‐resolution liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ‐LC‐MS/MS strategy to unravel the underlying mechanism of acupuncture. Methods: Wistar rats were subjected to vascular dementia with bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3 days after surgery. The Morris water maze was used to assess the cognitive function. Proteins were screened by quantitative proteomics and analyzed by bioinformatic analysis. Four differentially expressed proteins (DEPs) were validated by western blot. The reactive oxygen species (ROS) production, neuron cell loss, and long‐term potentiation (LTP) were determined after western blot. Results: Acupuncture at proper acupoints significantly improved cognitive function. A total of 31 proteins were considered DEPs. Gene ontology (GO) analysis showed that most of the DEPs were related to oxidative stress, apoptosis, and synaptic function, which were regarded as the major cellular processes related to acupuncture effect. Western blot results confirm the credibility of iTRAQ results. Acupuncture could decrease ROS production, increase neural cell survival, and improve LTP, which verified the three major cellular processes. Conclusion: Acupuncture may serve as a promising clinical candidate for the treatment of vascular dementia via regulating oxidative stress, apoptosis, or synaptic functions. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model. The protein and mRNA levels of Trx-1 and TrxR-1, the activity of TrxR-1 as well as the phosphorylation of the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway were measured by Western blot, real-time PCR analysis, TrxR-1 activity analysis and immunofluorescence (IF) staining respectively. We found that there were oxidative and apoptotic injury in the CA1 area, accompanied with the decreased expressions of Trx-1 and TrxR-1 in the hippocampus. Acupuncture ameliorated cognitive deficits caused by cerebral ischemic injury and inhibited oxidative stress and neuronal apoptotic injury in the hippocampus. Acupuncture also up-regulated the expressions of Trx-1 and TrxR-1, increased the activity of TrxR-1, accompanied with inhibiting the activation of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving cognitive function, inhibiting oxidative stress and neuron apoptotic damage were blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38 pathway. [ABSTRACT FROM AUTHOR]

Aims Oxidative stress and inflammation have been implicated in the pathogenesis of vascular dementia (VD). Thioredoxin-interacting protein (TXNIP) plays a vital role in oxidative stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation. There is evidence that acupuncture has an antioxidative and neuroprotective effect in VD. In this study, we investigated whether acupuncture can attenuate cognitive impairment via inhibiting TXNIP-associated oxidative stress and inflammation in VD rats. Methods Both common carotid arteries were occluded (2-vessel occlusion [2VO]) in rats to model VD. The neuroprotective effect of acupuncture was assessed by the Morris water maze and Nissl staining. Oxidative stress was assessed by detecting levels of reactive oxygen species, DNA oxidation, and antioxidase. Western blot, real-time PCR, and immunofluorescence were used to detect the expression of TXNIP, NLRP3, caspase-1, and IL-1β. A TXNIP siRNA intraventricular injection was applied to investigate whether acupuncture mimicked the effect of TXNIP inhibitor. Results Our findings demonstrated that VD rats treated with acupuncture had reduced hippocampal neuronal loss and oxidative stress. The upregulation of TXNIP, NLRP3, caspase-1, and IL-1β induced by 2VO was also reversed by acupuncture. Furthermore, TXNIP siRNA had a similar effect as acupuncture on cognition, hippocampal neurons, and ROS production in VD rats. Conclusion In conclusion, our study suggests that the neuroprotective effects of acupuncture in VD are mediated through reducing expression of TXNIP-associated oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is the second leading type of dementia after Alzheimer's disease plaguing the aging population. Acupuncture has served as alternative and complementary medicine in the world for a long time and its use for VaD is based on a large body of preclinical and clinical researches. The mechanisms that underlie the protective effects of acupuncture are slowly beginning to be understood. Acupuncture influences multiple aspects of the pathological process of VaD. It improves cognitive function through protecting cerebral neurons from oxidative stress, apoptosis, and neuroinflammation, regulating glucose metabolism and neurotransmitters. Acupuncture may also improve synaptic plasticity and blood vessel function. It is likely that no single factor can explain the protection provided by acupuncture. This review provides a comprehensive overview of established and recent findings in animal-based researches aiming to elucidate the complex mechanisms of acupuncture on VaD. [ABSTRACT FROM AUTHOR]

Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation. [ABSTRACT FROM AUTHOR]

Acupuncture has beneficial effects in vascular dementia (VaD) patients. The underlying mechanism, however, remains unknown. The present study was designed to investigate whether the cAMP/PKA/CREB cascade is involved in the mechanism of acupuncture in cerebral multi-infarction rats. In this study, cerebral multi-infarction was modeled in adult Wistar rats by homologous blood clot emboli. After a two-week acupuncture treatment at Zusanli (ST36), hippocampal-dependent memory was tested by employing a radial arm maze test. The hippocampus was isolated for analyses of cAMP concentration, phosphodiesterase (PDE) activity and CREB/pCREB and ERK/pERK expressions. The Morris water maze (MWM) task and CREB phosphorylation were evaluated in the presence of PKA-selective peptide inhibitor (H89). The radial arm maze test results demonstrated that acupuncture treatment at ST36 reversed hippocampal-dependent memory in impaired animals. Compared to those of the impaired group, cAMP concentration, PKA activity and pCREB and pERK expressions were increased following acupuncture therapy. Finally, the blockade of PKA reversed the increase in CREB phosphorylation and the improvement in recognitive function induced by acupuncture treatment. These results suggest that acupuncture could improve hippocampus function by modulating the cAMP/PKA/CREB signaling pathway, which represents a molecular mechanism of acupuncture for recognitive function in cerebral multi-infarction rats. [ABSTRACT FROM AUTHOR]

Background and Purpose: An ideal animal model to explore that pathogenesis and prevention of dementia is essential. The present study was designed to compare the difference of behavior and cerebral blood flow of the two vascular dementia rat models at different time intervals. Methods: The rats were randomly allocated to three groups: bilateral common carotid artery occlusion (BCCAO) group, thromboembolism (TE) group and sham-operated (SHAM) group. The performance in the Morris water maze (MWM) was analyzed at 7, 14 and 28 d after operation and cerebral blood flow (CBF) was analyzed at 28 days after operation. Result: The results showed that the two models exhibited longer latency, less times to crossing platform in MWM and lower CBF than the SHAM rats. Compared with the TE rats, the BCCAO rats have a significant prolongation of escape latency at 7 days and 28 days. In the probe trial, the BCCAO rats showed less number of times across the platform. Conclusion: The BCCAO rats maybe provide a more useful model to study the physiopathological mechanisms of cognitive impairment related to chronic cerebral ischemia. [ABSTRACT FROM AUTHOR]

After publication of this Article concerns have been raised about the overlap of Figure 1 with another article from the authors, which was not cited in the Article[1]. Retraction of: I Scientific Reports i https://doi.org/10.1038/srep17981, published online 10 December 2015 The Editors have retracted this Article. [Extracted from the article]

Data presented in Figure 1A was previously reported by the authors in Figure 1A of Reference[1], which is not cited in the Article. Correction to: I Scientific Reports i https://doi.org/10.1038/srep17981, published online 10 December 2015 This Article contains errors. [Extracted from the article]