Beneficial Effects Of Electroacupuncture Research Articles

Mechanism of electro-acupuncture in alleviating intestinal injury in septic mice via polyamine-related M2-macrophage polarization.

The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization. A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization. EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1β and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared. The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.

Effect of electroacupuncture at ST36 on the cerebral metabolic kinetics of rheumatoid arthritis rats

Electroacupuncture (EA) has been shown to enhance the recovery of symptoms in rheumatoid arthritis (RA); however, the underlying mechanism remains unclear. Both the pathogenesis of RA and the therapeutic effects of EA are closely associated with the metabolic activity of the brain. In this study, we investigated the effect of EA at the “Zusanli” acupoint (ST36) on a rat model of collagen-induced rheumatoid arthritis (CIA). The results demonstrated that EA effectively alleviated joint swelling, synovial hyperplasia, cartilage erosion, and bone destruction in CIA rats. Additionally, the metabolic kinetics study revealed a significant increase in the 13C enrichment of GABA2 and Glu4 in the midbrain of CIA rats treated with EA. Correlation network analysis showed that changes in Gln4 levels in the hippocampus were strongly associated with the severity of rheumatoid arthritis. Immunofluorescence staining of c-Fos in the midbrain’s periaqueductal gray matter (PAG) and hippocampus demonstrated increased c-Fos expression in these regions following EA treatment. These findings suggest that GABAergic and glutamatergic neurons in the midbrain, along with astrocytes in the hippocampus, may play vital roles in the beneficial effects of EA on RA. Furthermore, the PAG and hippocampus brain regions hold potential as critical targets for future RA treatments. Overall, this study provides valuable insights into the specific mechanism of EA in treating RA by elucidating the perspective of cerebral metabolism.

Electroacupuncture in promoting neural repair after spinal cord injury: Inhibiting the Notch signaling pathway and regulating downstream proteins expression.

Spinal cord injury (SCI) is one of the serious central nervous system injuries and the incidence of SCI continues to increase. Previous studies have indicated that electroacupuncture (EA) is beneficial for promoting recovery after SCI. In the present study, we attempted to evaluate how EA can promote the neural repair in SCI model rats by observing changes in the Notch signaling pathway. Experimental rats were randomly divided into four groups. Each group had its own intervention period: 1 day, 7 days, 14 days, and 28 days, and five randomized subgroups: blank control (B) group, blank electroacupuncture (BE) group, sham operation (S) group, model control (M) group and EA group. Animals in the EA group and the BE group were treated with EA at Dazhui (GV14) and Mingmen (GV4) acupoints for 20 min. After the intervention period, the Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neurological function. We found that BBB score increased in EA-treated groups. Hematoxylin and eosin staining was used to observe pathological changes in the injured spinal cord and the results showed that EA therapy could promote the repair of injured spinal cord tissue. Immunohistochemistry and Western blot methods were used to detect the expression of proteins Delta1, Presenilin1, Hes1, and Hes5 in the injured spinal cord. The results showed that the expression levels of Delta1, Presenilin1, Hes1, and Hes5 increased significantly after SCI and decreased after EA treatment. Our study suggested that the possible mechanism by which EA could benefit the recovery after SCI in rats may include inhibiting the Notch signaling pathway and regulating the downstream proteins expression. In addition, our study can provide reference for selecting acupoints and treatment cycle in the treatment of SCI.

Current Aspects Regarding the Clinical Relevance of Electroacupuncture in Dogs with Spinal Cord Injury: A Literature Review.

Simple SummaryThis review aims to provide an overview of the relevance of electroacupuncture in dogs with spinal cord injury. We illustrate and discuss the areas that have advanced in recent years and those that still require further research. Systematic studies have been conducted on Google Scholar, PubMed, Science Direct, Cab Direct, and Research Gate. This article is believed to be the first review of electroacupuncture in dogs with spinal cord injury. Electroacupuncture provides better analgesia than direct acupuncture by increasing spinal opioid release and increases blood supply to the spinal cord and nerve root. When combined together, Eastern and Western treatment offers faster recovery and improved ambulation and perception of deep pain than medical treatment results alone.In recent years, the use of acupuncture and electroacupuncture has been increasing as more clinical research has been conducted showing positive results in the treatment of animals, particularly dogs. Electroacupuncture is a more complex and specific acupuncture technique that involves electrical stimulation on acupuncture needles. Most of the studies have shown that the beneficial effects of electroacupuncture are more evident than in acupuncture alone. This review included studies focused only on dogs with spinal cord injury. Research facility animals (mice, rats, and rabbits) were avoided. Titles and abstracts of identified articles were read, and outlines were made to be better understood. Clinical applications are discussed and suggested in each section. When specialists use this method, electroacupuncture can be an excellent complementary therapy for veterinary patients’ pain control.

Electroacupuncture Ameliorates Cerebral I/R-Induced Inflammation through DOR-BDNF/TrkB Pathway.

The beneficial effects of electroacupuncture (EA) at Shuigou (GV26) and Neiguan (PC6) on poststroke rehabilitation are critically related to the activation of the delta-opioid receptor (DOR). The underlying anti-inflammatory mechanisms in DOR activation and EA-mediated neuroprotection in cerebral ischemia/reperfusion (I/R) injury were investigated in the current study. Cell proliferation and apoptosis were detected by morphological changes, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release, and TUNEL staining. The mRNA levels were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR), and the protein expression was measured by western blot or enzyme-linked immunosorbent assay (ELISA) in vitro. Infarct volume was examined by cresyl violet (CV) staining, neurologic recovery was assessed by neurological deficit scores, and pro- and anti-inflammatory cytokines were determined by immunofluorescence in vivo. DOR activation greatly ameliorated morphological injury, reduced LDH leakage and apoptosis, and increased cell viability. It reversed the oxygen-glucose deprivation/reoxygenation- (OGD/R-) induced downregulation of DOR mRNA and protein, as well as BDNF protein. DOR activation also reduced proinflammatory cytokine gene expression, including TNF-α, IL-1β, and IL-6, and at the same time, increased anti-inflammatory cytokines IL-4 and IL-10 in OGD/R challenged PC12 cells. EA significantly reduced middle cerebral artery occlusion/reperfusion- (MCAO/R-) induced infarct volume and attenuated neurologic deficit scores. It markedly increased the expression of IL-10 and decreased IL-1β, while sham EA did not have any protective effect in MCAO/R-injured rats. DOR activation plays an important role in neuroprotection against OGD/R injury by inhibiting inflammation via the brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) pathway. The neuroprotective efficacy of EA at Shuigou (GV26) and Neiguan (PC6) on cerebral I/R injury may be also related to the inhibition of inflammatory response through the DOR-BDNF/TrkB pathway.

Electroacupuncture Restores Locomotor Functions After Mouse Spinal Cord Injury in Correlation With Reduction of PTEN and p53 Expression.

Background: We previously showed that electroacupuncture (EA) at Jiaji points promotes expression of adhesion molecule L1 in spinal cord tissue after mouse spinal cord injury (SCI) and contributes to recovery of neural functions.Objective: We investigated the effects of EA on downstream signaling molecules of L1 and molecules relevant to apoptosis with the aim to understand the underlying molecular mechanisms.Methods: Female C57BL/6 mice were divided into a sham group, injury group, injury+acupuncture (AP) group and injury+EA group. We investigated the changes in cognate L1-triggered signaling molecules after SCI by immunofluorescence staining and immunoblot analysis.Results: Protein levels of phosphatase and tensin homolog (PTEN) and p53 were decreased by EA at different time points after injury, whereas the levels of phosphorylated mammalian target of rapamycin (pmTOR), p-Akt and phosphorylated extracellular signal-regulatedkinase (p-Erk) were increased. Also, levels of myelin basic protein (MBP) were increased by EA. AP alone showed less pronounced changes in expression of the investigated molecules, when compared to EA.Conclusion: We propose that EA contributes to neuroprotection by inhibiting PTEN and p53 expression and by increasing the levels of pmTOR/Akt/Erk and of MBP after SCI. These observations allow novel insights into the beneficial effects of EA via L1-triggered signaling molecules after injury.

Electroacupuncture Improves Baroreflex and γ-Aminobutyric Acid Type B Receptor-Mediated Responses in the Nucleus Tractus Solitarii of Hypertensive Rats.

Electroacupuncture (EA) has been reported to benefit hypertension, but the underlying mechanisms are still unclear. We hypothesized that EA attenuates hypertension, in part, through modulation of γ-aminobutyric acid (GABA) receptor function in the nucleus tractus solitarii (NTS). In the present study, the long-term effect of EA on GABA receptor function and expression was examined in the NTS of two-kidney, one-clip (2K1C) renovascular hypertensive rats. EA (0.1–0.4 mA, 2 and 15 Hz) was applied at Zusanli (ST36) acupoints overlying the deep fibular nerve for 30 min once a day for two weeks. The results showed that long-term EA treatment improved blood pressure (BP) and markedly restored the baroreflex response in 2K1C hypertensive rats. The increased pressor and depressor responses to microinjection of GABAB receptor agonist and antagonist into the NTS in the hypertensive rats were blunted by the EA treatment. Moreover, EA treatment attenuated the increased GABAB receptor expression in the NTS of hypertensive rats. In contrast, EA had no significant effect on the GABAA receptor function and expression in the NTS of 2K1C hypertensive rats. These findings suggest that the beneficial effects of EA on renovascular hypertension may be through modulation of functional GABAB receptors in the NTS.

Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway.

The protective role of electroacupuncture (EA) treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI) remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4) signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

Role of Wnt/β-catenin in the tolerance to focal cerebral ischemia induced by electroacupuncture pretreatment

Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/β-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/β-catenin in EA pretreatment-induced neuroprotection. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. Neuronal survival, cell apoptosis, and the Garcia neurological deficit scores were evaluated 24 h after reperfusion. Moreover, learning and memory deficits were assessed 24 h after reperfusion using the Morris water maze test. Finally, the expression of β-catenin and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were investigated in the presence and absence of the Wnt/β-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of β-catenin in the hippocampus 24 h after reperfusion. Moreover, EA pretreatment improved the neurological outcomes, decreased neuronal loss, inhibited apoptosis, and reversed learning and memory deficits following reperfusion. These beneficial effects of EA were attenuated by Dkk-1, which effectively reversed the expression of β-catenin. Furthermore, the administration of a Wnt/β-catenin agonist upregulated the expression of β-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/β-catenin plays a role in the protective effects of EA pretreatment against cerebral ischemia, thus providing evidence of a novel mechanism underlying EA-pretreatment-induced rapid tolerance to focal cerebral ischemia.

The Beneficial Effects of Electro-acupuncture at PC6 (Neiguan-point) of Gene and Protein Expressions of Classical Inward-rectifier Potassium Channels in Myocardial Ischemic Rats.

This study is aim to investigate the effect of electro-acupuncture at PC6 (Neiguan-point) on the gene and protein expressions of classical inward-rectifier potassium channels (Kir) in myocardial ischemia (MI) rats induced by isoproterenol (ISO). With ten for each one, 50 rats were divided into 5 groups which were control group, MI group, PC6 group, LU7 (Lieque-point) group and non-acupoint group. The control group was injected normal saline solution (85 mg/kg), the other groups were injected ISO (85 mg/kg). All the rats were injected once daily for two days and recorded electrocardiograms (ECGs) after every injection. Electro-acupuncture (EA) was operated at PC6, LU7 and non-acupoint respectively in the rats of PC6 group, LU7 group and non-acupoint group after twice injections. EA was performed to these three groups with disperse-dense wave (4-20 Hz), pulse amplitude of 14V, 20 mins a day remaining 7 days. The gene and protein expressions of Kir2.1, Kir2.2 and Kir2.3 were analyzed by Western Immunoblotting Technology (Western Blot) and Real-time Fluorescence Quantitative Polymerase Chain Reaction (RT-PCR). But it is regrettable that we did not detect meaningful gene and protein expressions Kir2.3, and the expressions of Kir2.1 and Kir2.2 in MI induced groups were lower [The gene and protein decreased 39.4 ± 27.3% and 38.7 ± 17.1% respectively.] than control group (P < 0.05). Compared with MI group, the results of PC6 group and LU7 group increased [PC6 group: the gene and protein increased 42.9 25.0% and 42.2 ± 10.0% respectively. LU7 group: the gene and protein increased 23.8 ± 50.1% and 21.1 ± 32.5% respectively.] obviously (P < 0.05) after EA, furthermore the expressions of PC6 group were higher [The gene and protein increased 15.4 ± 16.7% and 17.3 ± 60% respectively.] than LU7 group (P < 0.05). The results show that PC6 has a better positive effect than LU7 on MI rats, and the mechanism is probably that EA at PC6 can significantly increase the gene and protein expressions of Kir2.1 and Kir2.2.

Activation of STAT3 is involved in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptors in rats

Pretreatment with electroacupuncture (EA) attenuates cerebral ischemic injury through the endocannabinoid system, although the molecular mechanisms mediate this neuroprotection are unknown. It is well-known that signal transducer and activator of transcription 3 (STAT3) plays an essential role in cell survival and proliferation. Therefore, we investigated whether STAT3 is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after transient focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MACO) for 120min. The expression of pSTAT3(Ser727), which is necessary for STAT3 activation, was examined in the ipsilateral ischemic penumbra. Infarct volumes and neurological scores were evaluated at 72h after MACO in the presence or absence of the STAT3 inhibitor peptide (PpYLKTK). Neuronal apoptosis and the Bax/Bcl-2 ratio were also evaluated 24h after reperfusion. Our results showed that EA pretreatment significantly enhanced neuronal expression of pSTAT3(Ser727) in the ischemic penumbra 6h after reperfusion. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and decreased the Bax/Bcl-2 ratio following reperfusion. The beneficial effects of EA were attenuated by PpYLKTK administered 30min before MACO, and PpYLKTK effectively reversed the increase in pSTAT3(Ser727) expression. Furthermore, CB1R antagonist or CB1R knockdown with siRNA blocked the elevation of pSTAT3(Ser727) expression by EA pretreatment, whereas the two CB1R agonists increased STAT3 activation. In conclusion, EA pretreatment enhances STAT3 activation via CB1R to protect against cerebral ischemia, suggesting that STAT3 activation may be a novel target for stroke intervention.

Electroacupuncture confers beneficial effects through ionotropic glutamate receptors involving phosphatidylinositol-3 kinase/Akt signaling pathway in focal cerebral ischemia in rats

Aim of the studyWe investigated the molecular mechanisms underlying the beneficial effects of electroacupuncture (EA) to cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model. Materials and methodsEA stimulation (2Hz, 1mA) was needle-delivered for 30min at acupoints corresponding to Baihui (GV20) and Qihai (CV6) in men in MCAO rats and was analyzed by an infarct volume, Western blot and immunohistochemical assay. ResultsEA stimulations strongly reduced infarct volume and improved neurological outcome after stroke. When we focused on the glutamate-evoked excitotoxic injury with coupled pathways, N-methyl-d-aspartate receptor (NMDAR) NR2A and NR2B and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR2 subunit phosphorylation were significantly arrested by EA treatment in the parietal cortex of the brain. On the contrary, phosphatidylinositol-3 kinase (PI3K) and Akt phosphorylation markedly increased. Treatment of MCAO rats with the selective PI3K inhibitor LY-294002 to confirm the signaling pathway involved in EA neuroprotection revealed abrogated neuroprotective effects induced by EA. ConclusionThese results suggest that the beneficial effects of EA were associated with reduction of NMDAR and AMPAR phosphorylation and with activation of PI3K/Akt pathway. The PI3K/Akt pathway may mainly contribute to EA-induced neuroprotection after stroke.

Electroacupuncture Attenuates Ovalbumin-Induced Allergic Asthma via Modulating CD4(+)CD25(+) Regulatory T Cells.

A mouse pulmonary hypersensitivity experimental model that mimics human asthma was developed, and electroacupuncture (EA) treatment was shown to reduce allergic inflammatory processes. In addition, we also assessed whether the beneficial effects of EA on allergic asthma could be correlated with CD4+CD25+Foxp3+ regulatory T cells (Treg). Cellular profiles and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly decreased in the EA-treated groups when compared to the OVA and anti-CD25 Ab-injected (Treg depletion) groups. Furthermore, total BAL cells were reduced in the EA groups when compared to other groups. Interestingly, the population of CD4+CD25+Foxp3+Tregs in pneumonocytes increased in EA-treated group when compared to OVA and Treg depletion groups. These results imply that EA stimulation at ST 36 may affect CD4+CD25+Foxp3+ Treg in an OVA-induced experimental model and may enhance Treg function by suppressing other T cells and limiting the immune response.

Electro-acupuncture reduces the need for additional anesthetics in experimental studies

To evaluate the possible beneficial effects of electro-acupuncture in rats subjected to ketamine/xylazine (KX) intra-peritoneal (i.p.) anesthesia. Forty-eight male Wistar rats were distributed in four equal groups. All rats received i.p. injections of ketamine (90 mg/kg) +xylazine (10 mg/kg) anesthesia. Basal values group (control) rats (BV) received no additional treatment. The equivalent of the human right ST36 (Zusanli) and CV-12(Zhongwan) acupoints were chosen for needling and electrical stimulation. AC rats were needled with sterilized disposable stainless steel needles at right ST36 and CV12 acupoints; needles were retained for 30 minutes. EAC10 rats, after needle insertion as described, had electrodes connected to both needles and to an electro stimulator model NKL EL-608; pulsed square waves, 10 Hz, 10 mA, was applied for 30 minutes. EAC100 rats were submitted to EA as described. However, a greater frequency (100 Hz) was used. Thirty-seven rats remained under adequate anesthetic level during the experiment. However, maintenance anesthesia was required by 11 rats. Need for additional anesthesia decreased to 9.1% in EAC100 rats compared to BV (36.3%). Both the AC and the EAC10/100 prolong the anesthetic effect of the combination Ketamine-xylazine in rats, allowing longer duration of anesthesia with a lower dose of anesthetic, thereby reducing the occurrence of complications.