[Effects of acupuncture on hemorrhagic transformation and motor function in stroke patients after intravenous thrombolysis with rt-PA: a prospective cohort study].

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION: The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.

Acupuncture for Hypertension in Animal Models: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to summarize and evaluate the efficacy of acupuncture in hypertension animal study. METHODS: Studies were searched from six databases, including Medline, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, VIP information database, and Chinese Biomedical Literature Database. Study quality of each included study was evaluated according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, and the risk of bias was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were selected as outcomes. Meta-analyses were performed using Stata 12.0 software. The effect size was calculated by combining SBP/DBP/MAP data with the random effects model, respectively. RESULTS: 67 studies containing 1522 animals were included. According to the ARRIVE guideline, 8 items were assessed as poor and 4 items were assessed as excellent. According to the SYRCLE tool, all studies were judged as having high risk of bias. Compared with the hypertension group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. Similarly, compared with the sham-acupuncture group, the pooled results showed significant antihypertension effects of acupuncture for SBP, DBP, and MAP. CONCLUSION: Although pooled data suggested that the acupuncture group was superior to the hypertension group or sham-acupuncture group for SBP/DBP/MAP, the presentation of poor methodological quality, high risk of bias, and heterogeneity deserves cautious interpretation of the results.

[Effect of timing of acupuncture on limb dysfunction in patients with cerebral infarction: a multicenter prospective cohort pilot study].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture at different timings in acute stage for limb dysfunction in patients with cerebral infarction. METHODS: A total of 101 patients with cerebral infarction limb dysfunction were divided into an early exposure group (n=51) and a late exposure group (n=50) according to the time of first acupuncture treatment during the acute phase. SPSS 25.0 software was used to balance the baseline between the two groups, and 31 pairs of matched patients were included, including 31 cases in the early exposure group and 31 cases in the late exposure group. The two groups were treated with Xingnao Kaiqiao acupuncture at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5), Weizhong (BL 40), etc., once a day, and the course of treatment was not limited. In the early exposure group, acupuncture was started after 1 to 3 days of onset; in the late exposure group, acupuncture was started after 11 to 14 days of onset. The modified Rankin scale (mRS) grade was recorded before treatment, 30 and 60 days after onset; Fugl-Meyer assessment (FMA) grade was observed before treatment and 30 days after onset; the effect of acupuncture timing on the patients was analyzed by logistic analysis. RESULTS: Compared before treatment, the mRS grade at 30 and 60 days after onset in the early exposure group was improved (P<0.05), which was superior to the late exposure group (P<0.05); compared before treatment, the FMA grade at 30 days after onset in the early exposure group was improved (P<0.05), which was superior to the late exposure group (P<0.05). The timing of acupuncture was independently correlated with the disability status and the severity of motor dysfunction at 30 days after onset, and the disability status at 60 days after onset (P<0.05). Compared with the late exposure group, the possibility of becoming non-disabled at 30 days after onset (OR=22.882, 95%CI: 4.034-129.778), normal limb motor dysfunction (OR=22.320, 95%CI: 3.454-144.213) and non-disabled at 60 days after onset (OR=8.650, 95%CI: 2.437-30.696) in the early exposure group was increased. CONCLUSION: The timing of acupuncture is an independent factor affecting the disability status and limb motor dysfunction in patients with cerebral infarction, and the effect of early intervention may be better than late intervention.

Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics study.

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.

Acupuncture Rescues Cognitive Impairment and Upregulates Dopamine-ß-Hydroxylase Expression in Chronic Cerebral Hypoperfusion Rats.

Alteration of dopamine (DA) and noradrenaline (NA) contributes to cognitive function. Acupuncture has been shown to affect DA and NA in chronic cerebral hypoperfusion (CCH) rats. However, the effect of acupuncture on DA-ß-hydroxylase (DBH), the biosynthetic enzyme of NA, remains unknown. In CCH rats we established chronic hypoperfusion by bilateral common carotid artery occlusion (two-vessel occlusion, 2VO) and treated them with acupuncture. Acupuncture displayed beneficial effects on hippocampus-dependent memory impairments, including nonspatial and spatial memory. That is also reflected in hippocampus long-term-potentiation (LTP). Moreover, DBH expression in the hippocampus and DBH activity in cerebrospinal fluid were upregulated after acupuncture treatment. In conclusion, these in vivo findings suggest that acupuncture exerts a therapeutic effect on hippocampus-dependent memory and hippocampus LTP in CCH rats, which may be partially related to the modulation of DBH in the hippocampus.

Bee venom therapy: Potential mechanisms and therapeutic applications.

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems.

Acupuncture Prevents the Impairment of Hippocampal LTP Through ß1-AR in Vascular Dementia Rats.

It is widely accepted that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of vascular dementia (VD) patients. We have previously reported that acupuncture improved cognitive function in rats with VD. However, the mechanisms involved in acupuncture improving cognitive ability remain to be elucidated. The present study aims to investigate the pathways and molecules involved in the neuroprotective effect of acupuncture. We assessed the effects of acupuncture on hippocampal long-term potentiation (LTP), the most prominent cellular model of memory formation. Acupuncture enhanced LTP and norepinephrine (NE) levels in the hippocampus. Inhibition of the ß-adrenergic receptor (AR), but not the α-AR, was able to block the effects of acupuncture on hippocampal LTP. Furthermore, inhibition of ß1-AR, not ß2-AR, abolished the enhanced LTP induced by acupuncture. The expression analysis revealed a significant upregulation of ß1-AR and unchanged ß2-AR with acupuncture, which supported the above findings. Specifically, increased ß1-ARs in the dentate gyrus were expressed on neurons exclusively. Taken together, the present data supports a beneficial role of acupuncture in synaptic plasticity challenged with VD. A likely mechanism is the increase of NE and activation of ß1-AR in the hippocampus.

Applications of Acupuncture Therapy in Modulating Plasticity of Central Nervous System.

OBJECTIVE: Acupuncture is widely applied for treatment of various neurological disorders. This manuscript will review the preclinical evidence of acupuncture in mediating neural plasticity, the mechanisms involved. MATERIALS AND METHODS: We searched acupuncture, plasticity, and other potential related words at the following sites: PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and VIP information data base. The following keywords were used: acupuncture, electroacupuncture, plasticity, neural plasticity, neuroplasticity, neurogenesis, neuroblast, stem cell, progenitor cell, BrdU, synapse, synapse structure, synaptogenesis, axon, axon regeneration, synaptic plasticity, LTP, LTD, neurotrophin, neurotrophic factor, BDNF, GDNF, VEGF, bFGF, EGF, NT-3, NT-4, NT-5, p75NTR, neurotransmitter, acetylcholine, norepinephrine, noradrenaline, dopamine, monamine. We assessed the effects of acupuncture on plasticity under pathological conditions in this review. RESULTS: Relevant references were reviewed and presented to reflect the effects of acupuncture on neural plasticity. The acquired literatures mainly focused on neurogenesis, alterations of synapses, neurotrophins (NTs), and neurotranimitters. Acupuncture methods mentioned in this article include manual acupuncture and electroacupuncture. CONCLUSIONS: The cumulative evidences demonstrated that acupuncture could induce neural plasticity in rodents exposed to cerebral ischemia. Neural plasticity mediated by acupuncture in other neural disorders, such as Alzheimer's disease, Parkinson's disease, and depression, were also investigated and there is evidence of positive role of acupuncture induced plasticity in these disorders as well. Mediation of neural plasticity by acupuncture is likely associated with its modulation on NTs and neurotransmitters. The exact mechanisms underlying acupuncture's effects on neural plasticity remain to be elucidated. Neural plasticity may be the potential bridge between acupuncture and the treatment of various neurological diseases.

Acupuncture for patients with vascular dementia: a systematic review protocol.

INTRODUCTION: This systematic review protocol aims to provide the methods used to evaluate the effectiveness and safety of acupuncture therapy for treating vascular dementia. METHODS AND ANALYSIS: The following eight databases will be searched from inception to July 2017: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database. All randomised controlled trials in English or Chinese related to acupuncture for vascular dementia will be included. Outcomes will include change in cognitive function and activities of daily living. The incidence of adverse events will be assessed for safety evaluation. Study inclusion, data extraction and quality assessment will be performed independently by two reviewers. Assessment of risk of bias and data synthesis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Ethics approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through peer-reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42017071820.

Acupuncture Attenuates Renal Sympathetic Activity and Blood Pressure via Beta-Adrenergic Receptors in Spontaneously Hypertensive Rats.

The sympathetic nervous system, via epinephrine and norepinephrine, regulates ß-adrenergic receptor (ß-AR) expression, and renal sympathetic activation causes sustained increases in blood pressure by enhanced renin release. In this study, we aim to investigate the effect and underlying mechanism of acupuncture at Taichong (LR3) on renal sympathetic activity in spontaneously hypertensive rats. Unanesthetized rats were subject to daily acupuncture for 2 weeks. Mean blood pressure (MBP) and heart rate variability (HRV) were monitored at days 0, 7, and 14 by radiotelemetry. After euthanasia on the 14th day, blood and the kidneys were collected and subject to the following analyses. Epinephrine and norepinephrine were detected by ELISA. The expression of ß-ARs was studied by western blotting and PCR. The renin content was analyzed by radioimmunoassay. 14-day acupuncture significantly attenuates the increase of MBP. The HRV indices, the standard deviation of all normal NN intervals (SDNN), and the ratio of the low-frequency component to the high-frequency component (LF/HF) were improved following acupuncture. Renal sympathetic activation induced upregulation of epinephrine, norepinephrine, and renin content were attenuated by acupuncture. In addition, acupuncture decreased ß1-AR expression and improved ß2-AR expression. These results indicated that acupuncture relieves the increased MBP via the regulation of renal sympathetic activity and ß-ARs.

Acupuncture Attenuated Vascular Dementia-Induced Hippocampal Long-Term Potentiation Impairments via Activation of D1/D5 Receptors.

BACKGROUND AND PURPOSE: Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement. METHODS: Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily. The D1/D5 receptors antagonist SCH23390 was administered intraperitoneally 15 minutes before each acupuncture treatment. Morris water maze was examined after acupuncture. Long-term potentiation was studied by an electrophysiological technique. Dopamine and metabolites levels were detected by microdialysis and high-performance liquid chromatography from brain tissue. The expression of D1R and D5R was analyzed by immunofluorescence. RESULTS: Acupuncture remarkably reversed cognitive deficits in 2-vessel occlusion model (2VO) rats, and the acupuncture points Zusanli (ST36) and Baihui (GV20) were confirmed to be the most effective combination. Electrophysiological recording data showed that 2VO-induced impairments of long-term potentiation were prevented by acupuncture. In addition, acupuncture promoted the release of dopamine and its major metabolites in the hippocampus of 2VO rats. The immunofluorescence experiment showed that the decrease of D1R and D5R in hippocampal dentate gyrus region of 2VO rats was reversed by acupuncture. Furthermore, we found that the effects of acupuncture against 2VO-induced impairments in cognition and synaptic plasticity were abolished by SCH23390. CONCLUSIONS: Improvement in cognition and hippocampal synaptic plasticity induced by acupuncture was achieved via activation of D1/D5 receptors in 2VO rats.

Mechanisms of acupuncture on vascular dementia-A review of animal studies.

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.

Molecular Mechanisms of Vascular Dementia: What Can Be Learned from Animal Models of Chronic Cerebral Hypoperfusion?

Vascular dementia (VD) is defined as a progressive neurodegenerative disease of cognitive decline, attributable to cerebrovascular factors. Numerous studies have demonstrated that chronic cerebral hypoperfusion (CCH) is associated with the initiation and progression of VD and Alzheimer's disease (AD). Suitable animal models were established to replicate such pathological condition in experimental research, which contributes largely to comprehending causal relationships between CCH and cognitive impairment. The most widely used experimental model of VD and CCH is permanent bilateral common carotid artery occlusion in rats. In CCH models, changes of learning and memory, cerebral blood flow (CBF), energy metabolism, and neuropathology initiated by ischemia were revealed. However, in order to achieve potential therapeutic targets, particular mechanisms in cognitive and neuropathological changes from CCH to dementia should be investigated. Recent studies have shown that hypoperfusion resulted in a chain of disruption of homeostatic interactions, including oxidative stress, neuroinflammation, neurotransmitter system dysfunction, mitochondrial dysfunction, disturbance of lipid metabolism, and alterations of growth factors. Evidence from experimental studies that elucidate the damaging effects of such imbalances suggests their critical roles in the pathogenesis of VD. The present review provides a summary of the achievements in mechanisms made with the CCH models, permits an understanding of the causative role played by CCH in VD, and highlights preventative and therapeutic prospects.

Mechanisms of Acupuncture Effect on Alzheimer's Disease in Animal- Based Researches.

Alzheimer's disease is the most common type of dementia in the aging population worldwide. The etiology and treatment of Alzheimer's disease are still not very clear. Finding a new treatment is urgent due to the increasing population aging. Acupuncture has been practicing in China for more than 3000 years and reported to be beneficial in treating cognitive impairment of Alzheimer's disease. This paper reviews the recent development on the effect of acupuncture on Alzheimer's disease in animal-based researches. It is suggested that acupuncture improves cognitive function of Alzheimer's disease by regulating glucose metabolism, enhancing neurotransmission as well as reducing oxidative stress, Aß protein deposition, and neuronal apoptosis. However, it is still difficult to clarify which specific signaling pathway contributes to the acupuncture effect. Better designed studies are recommended to investigate the effects of acupuncture on Alzheimer's disease.