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    [Randomized clinical trials of early acupuncture treatment of limb paralysis in traumatic brain injury patients and its mechanism]. Guo Zi-Quan,Huang Yong,Jiang Hua,Wang Wen-Bin Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the clinical effect of early acupuncture treatment of limb paralysis in patients with traumatic brain injury (TBI) and changes of serum interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels, so as to explore its mechanism underlying improvement of TBI. METHODS:A total of 70 TBI inpatients were equally divided into a medication group and an acupuncture plus medication group according to a random number table. The medication contained intravenous drip of Mannitol Injection (125 mL, once every 8 h ) and Oxiracetam Injection (4 g, once a day). Starting 72 h after TBI, acupuncture therapy was applied to main points as Fenglong (ST40), Zusanli (ST36), Guanyuan (CV4), Baihui (GV20), Shuigou (GV26) and Fengchi (GB20), etc. The treatment was given once a day for total 28 days. Before and after the treatment, plasma IL-6, BDNF and NGF contents were detected using radioimmunoassay, the volume of the injured brain tissue was detected by using CT scan. The neurological deficit severity was evaluated by using Glasgow Coma Scale (GCS), and the degree of activity of daily living (ADL) ability was assessed by using simplified Fugl-Meyer assessment (FMA) scale, and modified Barthel index (BI), separately. RESULTS:After the treatment, the GCS score on day 28, FMA and ADL-BI scores on day 28 and 60 were significantly increased in both medication and acupuncture plus medication groups in comparison with their own pre-treatment (<0.05). The focal volume values of the injured brain were significantly decreased on day 14 and 28 in both groups compared with their own pre-treatment (<0.05). The therapeutic effect of acupuncture plus medication was obviously superior to that of simple medication in lowering focal injured volume on day 14 and 28, and in increasing FMA and ADL-BI scores on day 28 and 60 (<0.05). Compared with pre-treatment, the levels of plasma IL-6 on day 3, 7 and 14 were significant decreased, and those of plasma BDNF and NGF on day 3, 7 and 14 considerably increased in both groups in comparison with their own pre-treatment (<0.05). The therapeutic effect of acupuncture plus medication was evidently superior to that of simple medication in lowering IL-6 on day 3 and 7, and in increasing BDNF and NGF levels on day 3, 7 and 14 (<0.05). CONCLUSION:Early acupuncture treatment can significantly improve the TBI patient's limb motor function and daily life activities, which may be related with its effects in reducing the inflammation and increasing BDNF and NGF levels. 10.13702/j.1000-0607.180744
    Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia. Shi Guang-Xia,Wang Xue-Rui,Yan Chao-Qun,He Tian,Yang Jing-Wen,Zeng Xiang-Hong,Xu Qian,Zhu Wen,Du Si-Qi,Liu Cun-Zhi Scientific reports In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress. 10.1038/srep17981
    [Scalp-acupuncture improves neurological function by regulating expression of IL-10 mRNA, IL-6 mRNA and TNF-α of parahippocampal gyrus in cerebral ischemic rats]. Wang Jin-Hai,Du Xiao-Zheng,Zhang Ting-Zhuo,Li Xing-Lan,Zhao Min,Bao Ying-Cun,Yan Qi,Zhang Zhen-Chang,Jiang Hua,Tian Liang,Yuan Bo Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of scalp-acupuncture intervention on the expression of Interleukin (IL)-10 mRNA, IL-6 mRNA and tumor necrosis factor (TNF) - α in the parahippocampal gyrus of cerebral ischemia (CI) rats, so as to explore its molecular mechanisms underlying improvement of CI. METHODS:A total of 64 male SD rats were randomized into normal control, model, medication and scalp-acupuncture groups (=16 rats in each group). The focal CI model was established by middle cerebral artery occlusion. Intraperitoneal injection of Ammonium Pyrrolidine Dithiocarbamate (100 mg•kg•d) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS6), followed by twirling the needles at 100 cycles/min for 1 min, once again every 10 min during 20 min' needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0-4 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0-10 points) were assessed according to Longa's (1989) and Schabitz's (2004) methods, respectively. The expression levels of IL-10 mRNA and IL-6 mRNA were detected by fluorescence quantitative PCR, and the expression of TNF-α was detected by immunohistochemistry. RESULTS:After modeling, the neurologic deficit and neurological function scores and the expression levels of IL-10 mRNA, IL-6 mRNA and TNF-α protein in the parahippocampus were significantly increased in the model group than in the normal control group (<0.01). Following the intervention, the neurologic deficit and neurological function scores as well as IL-6 mRNA and TNF-α protein expression were significantly down-regulated in both scalp-acupuncture and medication groups (<0.05), and the expression of IL-10 mRNA was obviously increased (<0.05) relevant to the model group. CONCLUSION:Scalp-acupuncture can improve neurologic function in CI rats, which is related to its effects in up-regulating the expression of IL-10, then down-regulating the expression of IL-6 and TNF-α (reducing inflammatory response) in the parahippocampal gyrus. 10.13702/j.1000-0607.180046
    Effects of "nourishing liver and kidney" acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats. Xia Wen-Guang,Zheng Chan-Juan,Zhang Xuan,Wang Juan Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established. Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi (K103), Taichong (ST09) of both sides, for 30 min once daily every morning. The animals in the sham operation group and model group were conventionally fed in the cage, without any intervention therapy. The rats of each group were assessed with modified neurological severity scores (mNSS). The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd, 7th and 14th day. The Morris water Maze (MWM) test was used to evaluate the rats' learning and memory abilities on the 15th day after acupuncture. The animals in the acupuncture control group and sham operation group presented no neurological deficit. In the acupuncture group, the nerve functional recovery was significantly better than that in the model group at the 7th and 14th day after modeling. The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd, 4th and 5th day. The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group. At the each time point, the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture control group. In the acupuncture group, the expression levels of BDNF at the 7th and 14th day increased more significantly than those in the model group. In the acupuncture group, the expression levels of SYN at the each time point increased more significantly than those in the model group. The post-synaptic density (PSD) was significantly increased and the synapse cleft width was narrowed in the acupuncture group as compared with other groups. The synaptic curvatures were improved obviously in the acupuncture group in contrast to the model group. It was concluded that the "nourishing liver and kidney" acupuncture therapy has positive effects on behavioral recovery, as well as learning and memory abilities, probably by promoting the expression of BDNF and SYN, and synaptic structure reconstruction in the ipsilateral hippocampus after I/R in rats. The "nourishing liver and kidney" acupuncture therapy can promote the functional recovery in rats after cerebral ischemia injury. 10.1007/s11596-017-1727-7
    Effects of electroacupuncture on acute cerebral infarction. Si Q M,Wu G C,Cao X D Acupuncture & electro-therapeutics research The present paper is to study the effects of electroacupuncture (EA) on acute ischemic stroke patient and acute cerebral ischemic rat. In clinic, 42 acute ischemic stroke patients were randomly divided into 2 therapeutic groups: drug group and EA+ drug group. Neurological deficits of patients were evaluated before and after the treatment by Chinese Stroke Scale. The results showed that the acute ischemic stroke patients treated by drug or EA+ drug were all partially recovered, but the clinical functional recovery in EA+ drug group was significantly better than in the drug group (P < 0.01). In laboratory, the model of reversible middle cerebral artery occlusion (MCAO) was used in rats. The somatosensory evoked potential (SEP) was recorded before and after MCAO. EA was applied one hour after cerebral ischemia and once a day after reperfusion for 7 days in EA+ MCAO group. It was shown that the amplitude of P1-N1 wave of SEP before MCAO was 100%. After MCAO 30 min the P1-N1 wave of SEP on the ipsilateral side of MCAO was decreased to 2.2 +/- 3% (MCAO group), 1.9 +/- 2% (MCAO+ EA group); and then recovered to 25.5 +/- 14.1% (MCAO group), 58.6 +/- 27.2% (MCAO+ EA group) after 7 days of reperfusion following MCAO 2 hours. The above results indicated that EA could promote the recovery of neurological function in acute ischemic stroke patients and SEP on MCAO rats. 10.3727/036012998816356562
    The effect of low versus high frequency electrical acupoint stimulation on motor recovery after ischemic stroke by motor evoked potentials study. Kim Young Suk,Hong Jin Woo,Na Byung Jo,Park Seong Uk,Jung Woo Sang,Moon Sang Kwan,Park Jung Mi,Ko Chang Nam,Cho Ki Ho,Bae Hyung Sup The American journal of Chinese medicine Electrical acupoint stimulation (EAS) has been used to treat motor dysfunction of stroke patients with reportedly effective results. When we operate EAS treatment, we can modulate the intensity and frequency of stimulation. The purpose of this study is to evaluate the effect of different frequencies in treating motor dysfunction of ischemic stroke patients with EAS. The subjects of this study were 62 ischemic stroke patients with motor dysfunction in Kyunghee oriental medical center. They have been hospitalized after 1 week to 1 month from onset. They were treated with 2 Hz or 120 Hz EAS for 2 weeks, and had motor evoked potentials (MEPs) tests before and after 2 weeks of EAS treatment. We measured latency, central motor conduction time (CMCT) and amplitude of MEPs. After 2 weeks of treatment, we compared MEPs data of the affected side between the 2 Hz group and the 120 Hz group. The 2 Hz group showed more significant improvement than the 120 Hz group in latency, CMCT and amplitude (p = 0.008, 0.002, 0.002). In the case of the affected side MEPs data divided by normal side MEPs data, the 2 Hz group also showed higher improvement rate than the 120 Hz group in latency, CMCT and amplitude with significant differences (p = 0.003, 0.000, 0.008). These results suggest that low frequency EAS activates the central motor conduction system better than high frequency EAS, and EAS with low frequency could be more helpful for motor recovery after ischemic stroke than that with high frequency. 10.1142/S0192415X08005576
    Electroacupuncture reduces apoptotic index and inhibits p38 mitogen-activated protein kinase signaling pathway in the hippocampus of rats with cerebral ischemia/reperfusion injury. Lan Xiao,Zhang Xin,Zhou Guo-Ping,Wu Chun-Xiao,Li Chun,Xu Xiu-Hong Neural regeneration research Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury. To further identify the involved mechanisms, we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa's method. At 30 minutes before model establishment, p38 MAPK blocker SB20358 was injected into the left lateral ventricles. At 1.5 hours after model establishment, electroacupuncture was administered at acupoints of (LU5), (LI4), (ST36), and (SP6) for 20 minutes in the affected side. Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores, but no significant differences were determined among different interventional groups. Hematoxylin-eosin staining also showed reduced brain tissue injuries. Compared with the SB20358 group, the cells were regularly arranged, the structures were complete, and the number of viable neurons was higher in the SB20358 + electroacupuncture group. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assay showed a decreased apoptotic index in each group, with a significant decrease in the SB20358 + electroacupuncture group. Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group. There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group. These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway. A time period of 3 days could promote the repair of ischemic cerebral nerves. 10.4103/1673-5374.202944
    Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. Cui Guo-Hong,Wu Jing,Mou Fang-Fang,Xie Wei-Hua,Wang Fu-Bo,Wang Qiang-Li,Fang Jie,Xu Yan-Wu,Dong You-Rong,Liu Jian-Ren,Guo Hai-Dong FASEB journal : official publication of the Federation of American Societies for Experimental Biology Administration of exosomes derived from mesenchymal stromal cells (MSCs) could improve some neurologic conditions by transferring functional biomolecules to recipient cells. Furthermore, exosomes from hypoxic progenitor cells exerted better therapeutic effects in organ injury through specific cargoes. However, there are no related reports about whether exosomes derived from MSCs or hypoxia-preconditioned MSCs (PC-MSCs) could prevent memory deficits in Alzheimer disease (AD). In this study, the exosomes derived from MSCs or PC-MSCs were systemically administered to transgenic APP/PS1 mice. The expression of miR-21 in MSCs was significantly increased after hypoxic treatment. Injection of exosomes from normoxic MSCs could rescue cognition and memory impairment according to results of the Morris water maze test, reduced plaque deposition, and Aβ levels in the brain; could decrease the activation of astrocytes and microglia; could down-regulate proinflammatory cytokines (TNF-α and IL-1β); and could up-regulate anti-inflammatory cytokines (IL-4 and -10) in AD mice, as well as reduce the activation of signal transducer and activator of transcription 3 (STAT3) and NF-κB. Compared to the group administered exosomes from normoxic MSCs, in the group administered exosomes from PC-MSCs, learning and memory capabilities were significantly improved; the plaque deposition and Aβ levels were lower, and expression of growth-associated protein 43, synapsin 1, and IL-10 was increased; and the levels of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, TNF-α, IL-1β, and activation of STAT3 and NF-κB were sharply decreased. More importantly, exosomes from PC-MSCs effectively increased the level of miR-21 in the brain of AD mice. Additionally, replenishment of miR-21 restored the cognitive deficits in APP/PS1 mice and prevented pathologic features. Taken together, these findings suggest that exosomes from PC-MSCs could improve the learning and memory capabilities of APP/PS1 mice, and that the underlying mechanism may lie in the restoration of synaptic dysfunction and regulation of inflammatory responses through regulation of miR-21.-Cui, G.-H., Wu, J., Mou, F.-F., Xie, W.-H., Wang, F.-B., Wang, Q.-L., Fang, J., Xu, Y.-W., Dong, Y.-R., Liu, J.-R., Guo, H.-D. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. 10.1096/fj.201700600R
    Electroacupuncture enhances hippocampal NSCs proliferation in cerebral ischemia-reperfusion injured rats via activation of notch signaling pathway. Tao Jing,Chen Bin,Gao Yanling,Yang Shanli,Huang Jia,Jiang Xin,Wu Yayin,Peng Jun,Hong Zhenfeng,Chen Lidian The International journal of neuroscience The purpose of this study was to investigate the mechanisms by which electroacupuncture (EA) enhances hippocampal neural stem cells (NSCs) proliferation in cerebral ischemia-reperfusion (I/R) injured rats. A total of 72 male adult Sprague-Dawley rats were randomly divided into the sham operation control group (SC), the ischemia control group (IC) and the EA group. Middle cerebral artery occlusion (MCAO) was performed to establish the focal cerebral I/R injury model. Proliferation of hippocampal NSCs in cerebral I/R injured rats was determined by the Nestin immunohistochemical staining. Activation of the notch signaling pathway was detected by Western blotting and reverse transcription polymerase chain reaction analysis. The serum level of neurotrophic factors, e.g., the brain-derived neurotrophic factor (BDNF) and the Glial cell line-derived neurotrophic factor (GDNF), was measured using enzyme-linked immunosorbent assay (ELISA). The results showed that EA at Quchi (LI11) and Zusanli (ST36) acupoints significantly alleviated neurological deficits, reduced infarct volumes and promoted the proliferation of hippocampal NSCs in cerebral I/R injured rats. The crucial signaling molecules in the notch signaling pathway were activated and the secretion of BDNF and GDNF was increased upon EA. The protein and mRNA levels of Cyclin D1, Cdk4 and p-Rb were increased, while p21 and p27 transcripts were suppressed by notch signaling. These results suggest that the up-regulatory effect of EA on the notch signaling pathway and neurotrophic factor secretion may result in the promotion of NSCs proliferation and consequently a therapeutic effect on cerebral ischemia. 10.3109/00207454.2013.840781
    [Effect of Electroacupuncture on Expression of Cortical srGAP 1 and Cdc 42 in Rats with Focal Cerebral Infarction]. Dai En-ze,Long Fei,Gong Biao,Guo Quan-hu,Wang Ying,Zeng Zhi-hua Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of electroacupuncture (EA) intervention on the neurological function and the expression change of Slit-Robo GTPase-activating protein-1 (srGAP 1) and cell division-cycle 42 (Cdc 42) in the cortex of rats with cerebral ischemic injury (CIRI) , so as to explore the mechanism of EA in the management of cerebral infarction. METHODS:A total of 48 male Sprague Dawley (SD) rats were randomly and equally divided into control, model, non-acupoint EA and EA groups (n = 12/group). The CIRI model was established based on the modified Zea Longa method. EA intervention was applied for 30 min, once a day for 14 days. Modified neurologic severity scores (mNSS) were assessed on day 1,3,7 and 14 after mode- ling. Immunofluorescence assay was used to detect the immunoactivity and distribution of srGAP 1 and Cdc 42 in the cortical ischemic region. Western blot was employed to detect the expression of srGAP 1 and Cdc 42 in the affected cortex. RESULTS:The mNSS displayed that the neurological score in the EA group was significantly lower than that in the model group and non-acupoint EA group at the 7th d and 14th d (P<0. 01). Immunofluorescence results showed that cerebral srGAP 1 and Cdc 42 were ex- pressed mainly in the cytoplasm. The fluorescence intensity of srGAP 1 of the EA group was significantly lower than that of the model group and non-acupoint EA group(P<0. 01). Meanwhile the fluorescence intensity of Cdc 42 of the EA group was markedly higher than that in the model group and non-acupoint EA group(P<0. 01). Western blot assay indicated that the expression level of srGAP 1 in the model group was significantly higher than that of the control group( P<0. 01) ,and that of the EA group was much lower than those of the model group and non-acupoint EA group(P<0. 01). There was no significant difference of srGAP 1 expression levels between the non-acupoint EA group and the model group(P>0. 05). Additionally, the protein expression of Cdc 42 in the model group was slightly higher than that of the control group(P>0. 05), and that of the EA group was significantly higher than those of the model group and non-acupoint EA group(P<0. 01). There was no significant difference of Cdc 42 expression levels between the non-acupoint EA group and the model group(P>0. 05). CONCLUSION:Cerebral infarction induced increase of cerebral srGAP 1 and decrease of Cdc 42 can be reversed by acupoint EA intervention in CIRI rats, which may be responsible for its effect in improving impaired neurological function after cerebral infarction.
    Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats. Zhao Yu,Deng Bin,Li Yichong,Zhou Lihua,Yang Lei,Gou Xingchun,Wang Qiang,Chen Guozhong,Xu Hao,Xu Lixian Cellular and molecular neurobiology We have reported electroacupuncture (EA) pretreatment induced the tolerance against focal cerebral ischemia through activation of canonical Notch pathway. However, the underlying mechanisms have not been fully understood. Evidences suggest that up-regulation of hypoxia inducible factor-1α (HIF-1α) contributes to neuroprotection against ischemia which could interact with Notch signaling pathway in this process. Therefore, the current study is to test that up-regulation of HIF-1α associated with Notch pathway contributes to the neuroprotection of EA pretreatment. Sprague-Dawley rats were treated with EA at the acupoint "Baihui (GV 20)" 30 min per day for successive 5 days before MCAO. HIF-1α levels were measured before and after reperfusion. Then, HIF-1α antagonist 2ME2 and γ-secretase inhibitor MW167 were used. Neurologic deficit scores, infarction volumes, neuronal apoptosis, and Bcl2/Bax were evaluated. HIF-1α and Notch1 intracellular domain (NICD) were assessed. The results showed EA pretreatment enhanced the neuronal expression of HIF-1α, reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis, up-regulated expression of Bcl-2, and down-regulated expression of Bax after reperfusion in the penumbra, while the beneficial effects were attenuated by 2ME2. Furthermore, intraventricular injection with MW167 efficiently suppressed both up-regulation of NICD and HIF-1α after reperfusion. However, administration with 2ME2 could only decrease the expression of HIF-1α in the penumbra. In conclusion, EA pretreatment exerts neuroprotection against ischemic injury through Notch pathway-mediated up-regulation of HIF-1α. 10.1007/s10571-015-0203-9
    [Effects of electroacupuncture on neurological deficit and pathomorphologic lesion in the rat of focal cerebral ischemia]. Liu Zhe,Lai Xin-sheng Zhongguo zhen jiu = Chinese acupuncture & moxibustion OBJECTIVE:To probe into regularity of effects of electroacupuncture on focal cerebral infarction. METHODS:Focal cerebral ischemia model was established by middle cerebral artery heat-occlusion (MACO) method. Electroacupuncture was given at Dazhui (GV 14) and Baihui (GV 20). NSS was used for evaluation of neurological impairment, TTC staining method for detection of the infarct volume, and HE staining method for investigation of the pathomorphologic lesion of the brain. RESULTS:MCAO could induce neurologic impairment, cerebral infarction and cerebral pathological lesion in the rat, all of these changes could be cured spontaneously in varying degrees with prolongation of ischemic time, but electroacupuncture could relieve the lesions to a certain extents. CONCLUSION:Electroacupuncture can improve neurologic deficit impairment, reduce the volume of cerebral infarction and ischemic pathological lesion, early interfere of acupuncture and moxibustion is of very important clinical significance for treatment of ischemic apoplexy.
    A randomized controlled trial on the treatment for acute partial ischemic stroke with acupuncture. Hu H H,Chung C,Liu T J,Chen R C,Chen C H,Chou P,Huang W S,Lin J C,Tsuei J J Neuroepidemiology The effectiveness of acupuncture in acute stroke remains largely untested and unproved. A randomized, controlled trial was carried out to study the feasibility of acupuncture in combination with conventional supportive treatment for acute stroke patients. A total of 30 patients, aged 46-74, with the onset of symptoms within 36 h were enrolled into the study after appropriate screening. All patients gave informed consent. Basing on the same supportive treatment, patients were randomly assigned to a treatment with or without acupuncture. The procedure and acupoint selection were discussed and decided through several meetings of a group of senior acupuncture doctors in Taiwan. Acupuncture was applied 3 times/week for 4 weeks. During the study period, there were no problems in conducting this trial in terms of patient availability and acceptance, and physician cooperation. A significantly better neurologic outcome was observed in the acupuncture group on day 28 and day 90. The improvement in neurologic status was greatest in patients with a poor neurologic score at baseline. There were no important side effects except for one episode of dizziness related to acupuncture treatment. The data and results of this study will be used as a guideline for planning a full-scale clinical trial, e.g. sample size calculation, method of randomization with stratification of prognostic factors, choosing acupuncture points and technique of acupuncture. 10.1159/000110308
    Functional improvement by electro-acupuncture after transient middle cerebral artery occlusion in rats. Wang S J,Omori N,Li F,Jin G,Hamakawa Y,Sato K,Nagano I,Shoji M,Abe K Neurological research Functional recovery by the application of electro-acupuncture (EA) on different acupoints was investigated using a transient middle cerebral artery occlusion (MCAO) model in rat. Acupoints were Baihui (D20) plus Renzhong (D26) (MCAO + D group), and Hanyan (G4), Xuanlu (G5), Xuanli (G6), plus Qubin (G7) (MCAP + G group). Animals with EA treatment showed significant functional improvements from 12 days after the reperfusion against those without EA treatment. Among EA treated groups, MCAO + G showed a more significant recovery than MCAO + D. Infarct volume revealed the significant reduction in the EA treated groups especially in MCAO + G at 30 days. Immunohistochemical study showed a remarkable induction of vascular endothelial growth factor (VEGF) in astrocytes of the peri-infarct area at 30 days, more in EA treated groups than in groups treated with MCAO alone. These results suggest that the acupoints applied in this study are effective for the functional recovery, and an enhanced expression of VEGF may play a certain role in recovery process after stroke. 10.1179/016164103101201751
    [Observation of clinical effect of acupuncture on vascular dementia and its influence on superoxide dismutase, lipid peroxide and nitric oxide]. Lai X,Mo F,Jiang G Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine OBJECTIVE:To observe the clinical effect of electroacupuncture and acupuncture on vascular dementia (VaD) and the influence on superoxide dismutase (SOD), lipid peroxide (LPO) and nitric oxide (NO) levels. METHODS:Forty-six cases of VaD were randomly divided into two groups, the electroacupuncture group (EA group) and the acupuncture group (AP group). Assessment of Hasgawa's dementia scale (HDS), functional activities questionnaire (FAQ) and neurologic deficit scoring were done before and after treatment, and the changes on SOD, LPO and NO levels were observed. RESULTS:After treatment, in the EA group, the HDS elevated, the FAQ lowered, SOD increased and LPO and NO decreased significantly, as compared with before treatment, P < 0.01. But these parameters were not changed significantly in the AP group after treatment. The clinical symptoms were improved in both groups, but the reduction on neurologic deficit score was not significant. The total effective rate of the EA group was higher than that of the AP group. CONCLUSION:The immediate effect of electroacupuncture was superior to that of acupuncture, suggesting that the electroacupuncture was more effective in promoting the intelligence recovery than acupuncture.
    [Scalp-acupuncture Improves Neurological Function by Regulating Expression of NF-κB p 65 mRNA, IκB mRNA and IL-1 β and TNF-α in Parahippocampal Gyrus of Cerebral Ischemia Rats]. Wang Jin-Hai,Zhang Ting-Zhuo,Zhao Min,Bao Ying-Cun,Yan Qi,Zhang Zhen-Chang,Du Xiao-Zheng,Jiang Hua,Tian Liang,Yuan Bo,Li Xing-Lan Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of scalp-acupuncture intervention on the expression of parahippocampal factor-κB p 65 mRNA (NF-κB p 65 mRNA), IκB mRNA, interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in rats with cerebral ischemia (CI), so as to investigate its molecular mechanisms underlying improving CI by reducing inflammatory response. METHODS:A total of 64 SD rats were randomized into normal control, model, medication and scalp-acupuncture groups, with 16 rats in each group. The focal CI model was established by middle cerebral artery occlusion (MCAO). Intraperitoneal injection of Pyrrolidine Dithiocarbamate (100 mg•kg•d) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), followed by twirling the needles at 200 cycles/min for 1 min, once again every 10 min during 30 min's needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0-5 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0-10 points) were assessed according to Longa's (1989) and Schäbitz's (2004) methods, respectively. The expression levels of NF-κB p 65 mRNA and IκB mRNA in the parahippocampus gyrus tissue were detected by fluorescence quantitative reverse transcription-PCR, and IL-1 β and TNF-α proteins in the parahippocampus gyrus tissue were detected by immunohistochemistry. RESULTS:After modeling, the neurologic deficit and neurological function scores and the expression levels of NF-κB p 65 mRNA, IL-1 β and TNF-α in the parahip-pocampus were significantly increased in the model group than in the normal group (<0.01), while the expression of IκB mRNA was considerably down-regulated (<0.01). Following treatment intervention, the neurologic deficit and neurological function scores as well as NF-κB p 65 mRNA, and IL-1 β and TNF-α protein expression were significantly decreased in both scalp-acupuncture and medication groups compared with the model group (<0.05, <0.01), and the decreased expression of IκB mRNA was obviously increased (<0.05).. CONCLUSION:Scalp-acupuncture can improve neurologic function in cerebral ischemic rats, which is related with its effects in up-regulating the expression of IκB to inhibit the dissociation of NF-κB, then decreasing the expression of IL-1 β and TNF-α (reducing inflammatory response) in the parahippocampal gyrus tissue. 10.13702/j.1000-0607.170532
    Neuroprotective effect of electroacupuncture and upregulation of hypoxia-inducible factor-1α during acute ischaemic stroke in rats. Li Ce,Zhang Tingting,Yu Kewei,Xie Hongyu,Bai Yulong,Zhang Li,Wu Yi,Wang Nianhong Acupuncture in medicine : journal of the British Medical Acupuncture Society BACKGROUND:Acupuncture is a traditional method that has been widely used in various fields of medicine with therapeutic effect. However, evidence of effectiveness to support the application of electroacupuncture (EA) during the process of ischaemia is scarce. OBJECTIVES:To investigate dynamic changes in hypoxia-inducible factor (HIF)-1α expression as well as its association with neurological status in rats subjected to acute ischaemic stroke and EA intervention. METHODS:Forty adult male rats were randomly divided into three groups that received sham surgery (Control group, n=10) or underwent middle cerebral artery occlusion and EA (MCAO+EA group, n=15) or minimal acupuncture as a control treatment (MCAO+MA group, n=15). The rats in the MCAO+EA and MCAO+MA groups received EA or acupuncture without any electrical current, respectively, during 90 min of ischaemia. Rats in the Control group received the same surgical procedure but without MCAO. EA involved electrical stimulation of needles inserted into the quadriceps at 50 Hz frequency and 3 mA current intensity. Neurological status was evaluated on postoperative day 1, and cerebral infarction volume (IV) and HIF-1α expression 24 hours later. RESULTS:Neurological scores were improved and cerebral IV was decreased in the MCAO+EA group compared to the MCAO+MA group (both p<0.05). Moreover, HIF-1α expression was higher in the MCAO+EA group versus the MCAO+MA group (p<0.05). CONCLUSIONS:EA enhanced recovery of neurological function, decreased cerebral IV and increased HIF-1α expression in ischaemic rats. Further research is needed to determine whether EA is effective for stroke treatment through the stimulation of muscle contraction. 10.1136/acupmed-2016-011148
    [Penetrative Needling from "Baihui" (GV 20) to "Qubin" (GB 7) Antagonizes Inflammatory Injury in Rats with Cerebral Hemorrhage]. Chen Qiu-Xin,Zou Wei,Sun Xiao-Wei,Yu Xue-Ping,Dai Xiao-Hong,Niu Ming-Ming,Teng Wei,Bao Yu,Yu Wei-Wei,Ma Hui-Hui Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of penetrative needling of "Baihui" (GV 20) to "Qubin" (GB 7) on neurologic functions and expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and toll-like receptor 4 (TLR-4, involving in inflammatory reactions) in the tissue around the local cerebral hematoma in rats with intracerebral hemorrhage (ICH), so as to provide evidence for clinical treatment of ICH. METHODS:Fifty-four male Wistar rats were randomly divided into sham control, mo-del and acupuncture groups, and then further divided into three time-point subgroups(1,3,7 days after modeling, =6/subgroup). The ICH model was established by injection of the rat's autoblood (50 μL) into the putaman region (P:0.2 mm, R:3.5 mm) in a stereotaxic apparatus and confirmed by Berderson's neurologic examination grading system (0-3 points). The neurologic function was assessed by using Longa's scoring (5-points) and footfault asymmetry testing[footfault index=(contra faults-ipsi faults)/total steps in 2 min]. For penetrative needling, an acupuncture needle was inserted into GV 20 and controlled to advance to GB 7 on the affected side and retained for 30 min, once daily. The expression of TNF-α, IL-6 and TLR-4 in the cerebral tissue around the putaman was detected by immunohistochemistry. RESULTS:After penetrative needling stimulation, the increased Longa's score and footfault asymmetry score in ICH rats were significantly decreased on day 1, 3 and 7 after modeling (<0.01), suggesting an improvement of neurologic function after the treatment. Immunohistochemical staining outcomes of the cerebral tissue surrounding the autoblood injection site showed that the expression levels of TNF-α, IL-6 and TLR-4 proteins on day 1, 3 and 7 were considerably higher in the model group than in the control group (<0.01), and markedly lower in the acupuncture group than in the model group (<0.01), suggesting a suppression of the proinflammatory factors and TLR-4 levels around the locus of the brain after needling intervention. A positive correlation existed between the expression levels of TLR-4 and IL-6/TNF-α. CONCLUSIONS:Penetrative needling stimulation of GV 20 to GB 7 can reduce the levels of proinflammatory factors TNF-α and IL-6, and TLR-4 in the ICH tissues in rats with cerebral hemorrhage, which may contribute to its effect in improving neurological function.
    Resting-state Functional Magnetic Resonance Imaging Analysis of Brain Functional Activity in Rats with Ischemic Stroke Treated by Electro-acupuncture. Liang Shengxiang,Lin Yunjiao,Lin Bingbing,Li Jianhong,Liu Weilin,Chen Lidian,Zhao Shujun,Tao Jing Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association OBJECTIVE:To evaluate whether electro-acupuncture (EA) treatment at acupoints of Zusanli (ST 36) and Quchi (LI 11) could reduce motor impairments and enhance brain functional recovery in rats with ischemic stroke. MATERIALS AND METHODS:A rat model of middle cerebral artery occlusion (MCAO) was established. EA at ST 36 and LI 11was started at 24 hours (MCAO + EA group) after ischemic stroke. The nontreatment (MCAO) and sham-operated control (SC) groups were included as controls. The neurologic deficits of all groups were assessed by Zea Longa scores and the modified neurologic severity scores on 24 hours and 8 days after MCAO. To further investigate the effect of EA on infract volume and brain function, magnetic resonance imaging was used to estimate the brain lesion and brain neural activities of each group at 8 days after ischemic stroke. RESULTS:Within 1 week after EA treatment, the neurologic deficits were significantly alleviated, and the cerebral infarctions were improved, including visual cortex, motor cortex, striatum, dorsal thalamus, and hippocampus. Furthermore, whole brain neural activities of auditory cortex, lateral nucleus group of dorsal thalamus, hippocampus, motor cortex, orbital cortex, sensory cortex, and striatum were decreased in MCAO group, whereas that of brain neural activities were increased after EA treatment, suggesting these brain regions are in accordance with the brain structure analysis. CONCLUSION:EA at ST 36 and LI 11 could enhance the neural activity of motor function-related brain regions, including motor cortex, dorsal thalamus, and striatum in rats, which is a potential treatment for ischemia stroke. 10.1016/j.jstrokecerebrovasdis.2017.06.018
    Adult neurogenesis and acupuncture stimulation at ST36. Nam Min-Ho,Yin Chang Shik,Soh Kwang-Sup,Choi Seung-hoon Journal of acupuncture and meridian studies Although it was believed that the brain was incapable of regeneration after embryonic development, neurogenesis is now known to occur into adulthood. Adult neurogenesis has been demonstrated in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. Acupuncture has long been used to treat neurologic conditions, and recent reports suggest that neurogenesis may account for its beneficial effects. ST36 was the most often used acupoint in previous reports and was shown to enhance cell proliferation and neuronal differentiation. This acupoint may be linked to the brain through the primo vascular system, an anatomic structure thought to correspond to acupuncture meridians. This primitive vascular-like system appears to be involved in physiologic and pathologic processes by circulating substances throughout the body. The role of the primo vascular system as the link between the skin and brain underlying the beneficial effects of acupuncture requires further investigation. 10.1016/j.jams.2011.09.001
    Effects of GV20 acupuncture on cerebral blood flow velocity of middle cerebral artery and anterior cerebral artery territories, and CO2 reactivity during hypocapnia in normal subjects. Byeon Hyung-sik,Moon Sang-kwan,Park Seong-uk,Jung Woo-sang,Park Jung-mi,Ko Chang-nam,Cho Ki-ho,Kim Young-suk,Bae Hyung-sup Journal of alternative and complementary medicine (New York, N.Y.) OBJECTIVES:Acupuncture has been gaining popularity among practitioners of modern medicine as an alternative and complementary treatment. However, the mechanism of its therapeutic effect still remains uncertain. The present study chose the GV20 acupoint to evaluate acupoint effectiveness, hypothesizing that its stimulation induces cerebrovascular responses. DESIGN AND SETTING:The effects of GV20 acupuncture treatment on middle cerebral artery (MCA) and anterior cerebral artery (ACA) blood flow velocities, and CO(2) reactivity during hypocapnia were evaluated in 10 healthy male subjects (mean age 25.6 ± 0.8 years). Measurements were done at rest and during hypocapnia, and were repeated four times each at different cerebral artery territories with an interval of 1 week. MCA and ACA blood flow velocities were measured with a transcranial Doppler flowmeter. Blood flow velocity was corrected to 40 mm Hg of end-tidal CO(2) partial pressure (P(ETCO2)), and was expressed as CV40. CO(2) reactivity was measured as percent change in mean blood flow velocity/mm Hg P(ETCO2). RESULTS:Mean MCA and ACA blood flow velocities at rest, CV40, and CO(2) reactivity during hypocapnia increased significantly after GV20 acupuncture treatment, whereas mean arterial blood pressure and pulse rate at rest did not change significantly. The increases in MCA and ACA blood flow velocity were associated with improved CO(2) reactivity after GV20 acupuncture treatment. CONCLUSIONS:The data suggest that GV20 acupuncture treatment increases cerebral blood flow. The results of this small-scale study provide preliminary evidence for acupuncture effectiveness. 10.1089/acm.2010.0232
    Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass. Xu Tao,Li Wenjie,Liang Yiqun,Yang Zhonghua,Liu Jingdong,Wang Yejun,Su Nailun Pakistan journal of pharmaceutical sciences Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.
    An effectiveness study comparing acupuncture, physiotherapy, and their combination in poststroke rehabilitation: a multicentered, randomized, controlled clinical trial. Zhuangl L X,Xu S F,D'Adamo C R,Jia C,He J,Han D X,Lao L X Alternative therapies in health and medicine CONTEXT:Stroke is a leading cause of death and disability worldwide, being the third leading cause of death in the United States and the second and third most common causes of death in Chinese cities and rural areas, respectively. Evaluation of different rehabilitative modalities appears necessary to optimize treatment. OBJECTIVES:To compare acupuncture and physiotherapy for effectiveness and reliability in treating hemiplegic patients after stroke. DESIGN:The research team designed a multicentered, three-arm, randomized controlled trial. Power calculations revealed a targeted sample size of 310 participants. SETTING:The study took place at seven in-patient hospitals in China. PARTICIPANTS:The research team screened a total of 310 patients. Of that number, 274 completed the study, 15 did not meet the inclusion/exclusion criteria, and 21 dropped out. Adverse events were rare (less than 1%), mild, and temporary. INTERVENTION:The research team randomly divided participants into three groups that all received conventional care as needed-including psychological counseling, standard nursing care, and daily medical evaluation plus (1) acupuncture, (2) physiotherapy, or (3) acupuncture plus physiotherapy. The participants received treatments once a day, 6 days a week for 4 weeks. OUTCOME MEASURES:The research team evaluated all patients at baseline, after 2 weeks, and after 4 weeks using the Fugl-Meyer Assessment of Physical Performance (FMA), a modified Barthel Index (BI), and the Neurologic Defect Scale (NDS). RESULTS:No significant differences existed between the three groups at baseline. Compared to baseline, participants in all groups improved their FMA, BI, and NDS scores by the end of week 2 (P≤.05) and further improved by the end of week 4 (P≤.05) The study found no statistically significant differences in outcomes between the three groups after treatment (P>.05). CONCLUSION:Acupuncture plus conventional care was similar in effectiveness to physiotherapy treatment plus conventional care for poststroke rehabilitation. The study found no synergistic effects for the combination of acupuncture and physiotherapy in addition to conventional care; that combination of treatments was no more effective than either treatment by itself. The effectiveness and lack of adverse events associated with acupuncture in this study suggest that it may represent an additional treatment option for stroke patients.
    Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs). Cavalli Loredana,Briscese Lucia,Cavalli Tiziana,Andre Paolo,Carboncini Maria Chiara Evidence-based complementary and alternative medicine : eCAM Acupuncture therapy has been used to treat several disorders in Asian countries and its use is increasing in Western countries as well. Current literature assessed the safety and efficacy of acupuncture in the acute management and rehabilitation of patients with neurologic disorders. In this paper, the role of acupuncture in the treatment of acute severe acquired brain injuries is described, acting on neuroinflammation, intracranial oedema, oxidative stress, and neuronal regeneration. Moreover, beneficial effects of acupuncture on subacute phase and chronic outcomes have been reported in controlling the imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence of neurovegetative crisis. Moreover, acupuncture may have a positive action on the arousal recovery. Further work is needed to understand the effects of specific acupoints on the brain. Allegedly concurrent neurophysiological measurements (e.g., EEG) may help in studying acupuncture-related changes in central nervous system activity and determining its potential as an add-on rehabilitative treatment for patients with consciousness disorders. 10.1155/2018/8107508
    Attenuating Ischemic Disruption of K Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment. Chao Dongman,Wang Qinyu,Balboni Gianfranco,Ding Guanghong,Xia Ying Molecular neurobiology Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K homeostasis in the neonatal cortex. Since maintaining cellular K homeostasis and inhibiting excessive K fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy. 10.1007/s12035-015-9621-4
    The effects of acupuncture and traditional Chinese medicines on apoptosis of brain tissue in a rat intracerebral hemorrhage model. Chen Jui-Chu Physiology & behavior OBJECTIVE:This study aimed to evaluate the effects of Chinese herbs and acupuncture on the neuronal apoptosis and the expression of apoptosis-related genes in the brain tissue of rats following intracerebral hemorrhage (ICH). METHODS:Collagenase VII was injected into the caudate nucleus of Sprague-Dawley rats to induce ICH. Chinese herbs (musk, borneol and tetrandrine) were intragastrically administered, and acupuncture was performed using Dazhui, Fengfu and Shuigou acupoints. Each group was further subdivided into 4 subgroups based on treatment duration (6-hour, 24-hour, 72-hour, and 1-week). Neurological impairment score, TUNEL assay and apoptotic markers, BCL-2, BAX, and caspase-3 were used to evaluate the apoptosis status after ICH and subsequent treatment. RESULTS:Chinese herbal therapy and acupuncture improved neurological impairment compared with no therapy and sham-operated animals. Significant differences in TUNEL positive cells were found between treatment groups (p < 0.001) and over time (p < 0.001). Differential expression of BCL-2, BAX, and caspase-3 was observed between treatment groups (p = 0.014 for BAX and < 0.05 for BCL-2 and caspase-3) and treatment duration groups (p = 0.006 for BAX and < 0.05 BCL-2 and caspase-3). CONCLUSIONS:Results indicate that Chinese herbs and acupuncture may improve neural impairment and reduce apoptosis, although there was no difference between therapies in a rat model of ICH. Additional experiments are needed to further clarify the role of these therapies following ICH. 10.1016/j.physbeh.2015.07.036
    [Mechanism of "" acupuncture for the opening of ATP sensitive potassium channel against cerebral ischemia reperfusion injury in rats]. Han Lin,Gao Yang,Wang Xuhui,Zhang Yanan,Zhang Xiangyu Zhongguo zhen jiu = Chinese acupuncture & moxibustion OBJECTIVE:To observe the mechanism of "" acupuncture for the opening of ATP sensitive potassium channel (K) against cerebral ischemia reperfusion injury in rats. METHODS:Eighty-four rats were randomly divided into a sham-operation group, a model group, an electroacupuncture (EA) group, an EA+K blocker group, 21 rats in each group. 10 μL intracerebral injection with glipizide (1 μmol/5 μL) was used in the EA+K blocker group. The cerebral ischemia reperfusion model was established by Zea Longa's suture method in the model group, the EA group and the EA+K blocker group. Rats in the sham-operation group were received the same surgery but without nylon filament insertion. Acupuncture (20 min a time) was performed at "Neiguan" (PC 6), "Shuigou" (GV 26) and "Sanyinjiao" (SP 6) in the EA group and the EA+K blocker group at 10:00 and 16:00 for 3 days, firstly 90 min after model establishment. EA (2 Hz/15 Hz, 1 mA) was connected at the affected "Neiguan" (PC 6) and "Sanyinjiao" (SP 6). The same fixation was used in the sham-operation group and the model group, without EA. Neurological function was assessed by Zausinger's neurologic assessment scale. 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume. Neurocyte apoptosis in the hippocampus was detected by flow cytometry and the protein expressions of B lymphocytoma-2 gene (Bcl-2) and B cell lymphoma factor-associated X protein (Bax) were measured by Western-blot. RESULTS:In comparison with the model group, the neurological score of the EA group increased (<0.01); the infarction volume and the hippocampal neuron's total apoptosis rate of the EA group decreased (both <0.05); the protein expression of Bcl-2 and Bcl-2/Bax of the EA group increased (<0.05, <0.01); and the protein expression of Bax of the EA group decreased (<0.01). Compared with the EA group, the neurological score of the EA+K blocker group decreased (<0.05); the total apoptosis rate of hippocampus neurons of the EA+K blocker group increased (<0.05); the expression of Bcl-2 protein of the EA+K blocker group reduced (<0.05); the expression of Bax protein of the EA+K blocker group increased (<0.05). CONCLUSION:"" acupuncture has brain protective effect on rats with focal cerebral ischemia reperfusion injury. The mechanism may be related to regulating the opening of K channels and decreasing the apoptosis of neurons. 10.13703/j.0255-2930.2018.12.017
    Acupuncture for acute moderate thalamic hemorrhage: randomized controlled trial study protocol. Wang Chengwei,You Chao,Ma Lu,Liu Mengyue,Tian Meng,Li Ning BMC complementary and alternative medicine BACKGROUND:Thalamic hemorrhage (TH) is a neurological insult with a high rate of morbidity and mortality. Moderate TH (10-30 ml) accounts for more than half of all TH. Treatment remains controversial. The role of acupuncture in patients with moderate TH is not clear. METHODS:We will conduct a single-center, randomized, parallel group, and assessor-blinded clinical trial. A total of 488 patients with moderate TH will be randomly assigned to one of eight groups: 10-15 cc left sided TH study group (N = 61) and a corresponding control group (N = 61), 10-15 cc right sided TH study group (N = 61) and a corresponding control group, 15-30 cc left sided TH study group (N = 61) and a corresponding control group (N = 61), and 15-30 cc right sided TH study group (N = 61) and a corresponding control group. Study groups will receive acupuncture in addition to standard treatment, while control groups will receive standard treatment alone. The primary outcome will be change in National Institutes of Health Stroke Scale scores at 30 and 90 days after TH. The secondary outcomes will be death or major disability, defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90-days, need for surgery at 30-days, Glasgow Outcome Scale (GOS) score at 90-days following TH onset, and the results of several additional group specific tests. The rate of adverse events will then be compared between the groups. DISCUSSION:This study will attempt to answer the question of whether or not acupuncture can improve neurologic outcome following moderate TH.  TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR-IOR-16008362). 10.1186/s12906-017-1614-6
    A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke. Wang Wen-wen,Xie Cheng-long,Lu Lin,Zheng Guo-qing Scientific reports Acupuncture for stroke has been used in China for over 2,000 years and nowadays is increasingly practiced elsewhere in the world. However, previous studies had conflicting findings on the results of acupuncture. Here, we conducted a systematic review and meta-analysis to assess the current evidence for the effect of Baihui (GV20)-based scalp acupuncture in animal models of focal cerebral ischemia. Six databases from the inception of each database up to June 2013 were electronically searched. Primary outcomes were infarct size and neurobehavioral outcome. Ultimately, 54 studies involving 1816 animals were identified describing procedures. Meta-analysis results showed that twelve studies reported significant effects of Baihui (GV20)-based scalp acupuncture for improving infarct volume compared with middle cerebral artery occlusion group (P < 0.01), and thirty-two studies reported significant effects of Baihui (GV20)-based scalp acupuncture for improving the neurological function score when compared with the control group (P < 0.01). In conclusion, Baihui (GV20)-based scalp acupuncture could improve infarct volume and neurological function score and exert potential neuroprotective role in experimental ischemic stroke. 10.1038/srep03981
    [Development of Researches on Scalp Acupuncture for Ischemic Stroke]. Tian Liang,Wang Jin-hai,Sun Run-jie,Zhang Xing-hua,Yuan Bo,Du Xiao-zheng Zhen ci yan jiu = Acupuncture research Ischemic stroke is one of the commonly met diseases in clinical practice nowadays. Acupuncture therapy is widly used in the treatment of sequela of ischemic stroke in China and its mechanisms have been extensively studied in recen years. In the present paper, the authors focus on the development of studies on the mechanism of scalp acupuncture therapy in the treatment of ischemic stroke. Results indicate that scalp acupuncture intervention can 1) improve cerebral blood circulation to promote regional energy metabolism, 2) up-regulate expression of glial cell-line derived neurotrophic factor (GDNF), etc., possibly promoting proliferation and differentiation of neural stem cells in the focal cerebral cortex and hippocampus, 3) reduce contents of excitatory amino acid and increase level of gamma-aminobutyric acid (GABA) to lower neurogenic toxicity, and relieve cerebral injury, 4) ease cerebral vascular immunoinflammatory reactions, 5) regulate blood lipid metabolism to resist cerebral free radical damage, and 6) inhibit cerebral cortical apoptosis. However, these results only revealed very limited intrinsic mechanisms of scalp acupuncture in improving ischemic stroke. Further studies using comprehensive techniques of multi-disciplines as molecular biology, electrophysiology, etc. are definitely needed.
    [Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia]. Wang Zhuo-Yu,Ma Jia-Jia,Guan Han-Yu,Tian Yao,Ren Xiu-Jun,Ma Hui-Fang Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to reveal its mechanisms underlying improvement of HL-CI. METHODS:Forty-five rats were randomly divided into normal control,sham operation,model,EA group I(EA+MA was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA group Ⅱ (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each group. The HL-CI model was established by feeding the animals with high fat forage for 6 weeks and then making an occlusion of the unilateral middle cerebral artery by regional application of quantitative paper adsorbing 50% FeCl solution (10 μL). Rats of the sham operation group were treated with the same procedures only without application of FeCl solution. For rats of the EA group I,EA (1-3 mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20 min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was conducted once daily for 7 days after CI modeling. For rats in the EA group Ⅱ, EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI modeling. The neurological impairment was assessed by Zea Longa's scoring. The blood sample was taken from the abdominal aorta for measuring the contents of serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological changes of the cerebral cortex were observed after H.E. staining, and the expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry. RESULTS:Following modeling,the neurological score,CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells as well as Caspase-3 immunoactivity level were significantly increased in the model group(<0.05), while serum HDL-C level was obviously decreased(<0.05). After the treatment,the increased neurological score, CHO, TG and LDL-C contents, and the number of Caspase-3 positive cells and Caspase-3 immunoactivity level were considerably decreased in the EA group I and Ⅱ(<0.05)while the decreased HDL-C level was notably increased relevant to the model group(<0.05). The effects of the EA group I were notably superior to those of EA group Ⅱ in down-regulating the neurological score,CHO, TG and LDL-C levels and the expression of Caspase-3 protein(<0.05). No significant differences were found between the normal control and sham operation groups in the neurological scores 20 min and 7 days after modeling and Caspase-3 expression levels (>0.05). H.E. staining showed a reduction of the apoptotic cells and inflammatory cells in both EA group I and Ⅱ. CONCLUSIONS:Both EA and EA+MA interventions can improve neurological function in HL-CI rats,which may be related to their effects in adjusting the levels of serum lipids and down-regulating the expression of cell apoptosis-related Caspase-3 protein in the ischemic cortex. Moreover, the cerebral ischemia injury may be lightened by EA-lowering hyperlipemia first.
    [Influence of electroacupuncture intervention on hippocampal IL-1beta content and I kappa B kinase beta expression in focal cerebral ischemia/reperfusion rats]. Qin Wen-Yi,Luo Yong,Yu Chao Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effect of electroacupuncture (EA) of "Baihui" (GV 20) and left "Hegu" (LI 4)-"Taichong" (LR 3) on levels of hippocampal IL-1beta content and I kappa B kinase (IKK) beta protein in focal cerebral ischemia/reperfusion (CI/R) injury rats so as to reveal its mechanism underlying improvement of cerebral ischemia. METHODS:One hundred and ninety-eight male SD rats were randomly divided into sham group (n = 54), model group (n = 72) and EA group (n = 72) which were further randomized into 12 h, 24 h and 48 h subgroups according to the duration of CI/R. The focal CI/R injury model was established by middle cerebral artery occlusion (MCAO) and reperfusion. EA (1 mA, 2 Hz/100 Hz) was applied to "Baihui" (GV 20) and the left "Hegu" (LI 4)-"Taichong" (LR 3) for 20 min, once every 12 h. The level of IL-1beta content in the right hippocampus tissue was detected by ELISA and the expression levels of hippocampal IKKbeta protein were detected by immunohistochemistry and Western blot, respectively. RESULTS:Compared with the 3 subgroups of the sham group, the levels of hippocampal IL-1beta contents at time-points of 12 h, 24 h and 48 h after MCAO were significantly increased in the model group (P < 0.01). In comparison with the model group, the contents of hippocampal IL-beta at the 3 corresponding time-points in the EA group were significantly reduced (P < 0.01). The expression levels of hippocampal IKKbeta protein at the 3 time-points after MCAO shown by immunohistochemistry and Western blot analysis were significantly higher in the model group than in the sham group (P < 0.05), and considerably lower in the EA group than in the model group (P < 0.05). CONCLUSION:EA of GV 20 and LI 4-LR 3 can obviously reduce CI/R injury induced increase of IL-1beta content and IKKbeta expression level in the hippocampus, which may be responsible for its effect in alleviating cerebral infarction by reducing inflammatory injury in the hippocampus.
    [Effects of acupuncture of "Baihui"(GV 20) and "Zusanli"(ST 36) on expression of cerebral IL-1beta and TNF-alpha proteins in cerebral ischemia reperfusion injury rats]. Chen Su-Hui,Sun Hua,Xu Hong,Zhang Ya-Min,Gao Yang,Li Sha Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the effects of acupuncture of "Baihui" (GV 20) and "Zusanli" (ST 36) on the expression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha proteins in the bilateral cerebral tissue in cerebral ischemia reperfusion injury (CI/RI) rats, so as to explore its mechanism underlying improving CI. METHODS:Seventy-eight SD rats were randomized into sham-operation (control) group (n = 6), model group (n = 36) and acupuncture group (n = 36), and the latter two groups were further divided into 12, 24, 48, 72, 96 and 144 h subgroups (n = 6 in each subgroup) according to the reperfusion time. Acupuncture stimulation was applied to GV 20 and left ST 36 for 20 min at the required time-points after successful operation, once a day. The expression of IL-1beta and TNF-alpha in bilateral brain tissue was examined by immunohistochemistry. RESULTS:Immunohistochemical staining showed that the expression of cerebral IL-1beta protein in cerebral ischemia regions exhibited a double-peak, and the peak time in the model group was at 48 h and 96 h, while the expression of TNF-alpha protein in cerebral ischemia regions exhibited a single-peak, and the peak time in both model and acupuncture groups was at 72 h. In comparison with the normal group and sham group, cerebral IL-1beta and TNF-alpha protein expression levels of both ischemic and non-ischemic regions were increased significantly in the model group (P < 0.05). Compared to the model group, the expression levels of cerebral IL-1beta and TNF-alpha of both ischemic and non-ischemic regions in the acupuncture group at most of the time-points after CI/RI were decreased obviously (P < 0.05). CONCLUSION:Acupuncture can effectively suppress the expression of IL-1beta and TNF-alpha proteins in bilateral ischemic and non-ischemic cerebral regions in CI/RI rats,suggesting an anti-inflammatory effect of acupuncture intervention.
    [Influence of acupuncture intervention on neurologic deficits, cerebrocortical cell apoptosis and Protein kinase A expression in rats with focal cerebral ischemia]. Li Zhan-Biao,Liu Fang-Ming,Liu Wei-ju Zhen ci yan jiu = Acupuncture research OBJECTIVE:To observe the influence of acupuncture intervention on expression of protein kinase A (PKAP in the cerebrocortex of rats with focal cerebral ischemia-reperfusion injury(CI/RI), so as to explore its underlying neuroprotection mechanism on cerebral ischemia. METHODS:Ninety male SD rats were randomly and evenly divided into sham-operation (sham), model and acupuncture groups which were further randomized into 3, 7 and 14-days (d) subgroups (10 rats/subgroup). CI/RI model was established by occlusion of the left middle cerebral artery for 2 hours and reperfusion. Manual acupuncture stimulation was applied to "Baihui" (GV 20) and "Shuigou" (GV 26), as well as the right "Quchi" (LI 11), "Hegu" (LI 4), "Neig (PC 6), "Zusanli" (ST 36),"Sanyinjiao"(SP 6) and "Taichong" (LR 3) for 30 min, once daily for 3, 7 and 14 d respectively. Rats of the sham and model groups were restrained for 30 min each day. Neurological defects were assessed by ethologic scoring according to Bederson's neurologic assessment scales. Cellular apoptosis in the ischemic cortex was detected by flow cytometry and PKA expression determined by immunohistochemistry for calculating its PKA immunoreaction (IR)-positive cell rate, respectively. RESULTS:Compared with the sham group, the neurologic scores, cortical cellular apoptosis rates and PKA IR-positive cell rates of the model group were significantly increased at the time-points of day 3, 7 and 14 post-treatment (P<0. 05). In comparison with the model group, the neurologic scores and cortical cellular apoptosis rates of the acupuncture group at the time-points of day 3, 7 and 14 post-treatment were considerably down-regulated (P<0. 05), and the cortical PKA IR-positive cell rates of the acupuncture group were remarkably increased (P<0. 05). In addition, along with the increase of acupuncture treatment sessions, lower apoptosis rates and more PKA IR-positive cells were found, suggesting a cumulative effect. CONCLUSION:Acupuncture intervention can lower cellular apoptosis rate of the ischemic cerebrocortex and up-regulate cortical PKA expression level in CI/RI rats, which may be responsible for its effect in improving neurologic deficits.
    Immediate effects of acupuncture on the mechanosensitivity of the median nerve: an exploratory randomised trial. Morais Nuno,Greten Henry Johannes,Santos Maria João,Machado Jorge Pereira Acupuncture in medicine : journal of the British Medical Acupuncture Society BACKGROUND:Acupuncture appears to reduce the mechanosensitivity of peripheral nerves in animal models; yet, this possibility has not been demonstrated in humans. OBJECTIVES:The main objective of this exploratory trial was to evaluate the immediate effects of acupuncture on the mechanosensitivity of the median nerve, measured by the elbow extension range-of-motion (EE-ROM) at pain onset and maximum tolerance during the upper limb neurodynamic test 1 (ULNT1). Additional objectives were to test the effects of two different points in ULNT1 responses and critically appraise pre-/post-intervention changes for conducting future research. METHODS:Thirty-one asymptomatic individuals, randomly assigned to the PC group (n=14) or the LU group (n=17) by the coin flip procedure, underwent acupuncture (leopard spot needling) at PC5 or LU5'', respectively. Two-way mixed-model analysis of variance (ANOVA) with time (pre-intervention vs post-intervention) as the within-subject factor and group (PC vs LU) as the between-subject factor, plus time×group interaction, were used to determine the effects of acupuncture therapy on EE-ROM at pain onset and maximum tolerance during ULNT1. RESULTS:At baseline there were no differences between groups (p>0.05). After acupuncture, mean EE-ROM increased 3.1° at pain onset (p=0.029, 0.154) and 5.6° at maximum tolerance (p=0.002, 0.277) with no differences between groups (p>0.05, 0.01). CONCLUSION:Immediately after acupuncture, the mechanosensitivity of the median nerve appears to be reduced as observed by an increase in EE-ROM during the ULNT1. Further studies are needed to confirm these preliminary findings. TRIAL REGISTRATION NUMBER:NCT02150915; Post-results. 10.1136/acupmed-2016-011357