Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus

Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Effectiveness and safety of electroacupuncture analgesia in controlling intraoperative pain and hemodynamics during total thyroidectomy:A randomized controlled trial

Objective:To evaluate the effectiveness and safety of electroacupuncture in conjunction with additional medications in providing analgesia and stabilizing hemodynamic parameters during total thyroidectomy.Methods:This randomized controlled trial included 100 patients who underwent a total thyroidectomy between October 2022 and October 2023 at the Vietnam National Hospital of Acupuncture.The patients were randomized into two groups.The electroacupuncture analgesia(EA)group received EA stimulation at five acupuncture points:Hegu(LI 4),Neiguan(PC 6),Shuitu(ST 10),Quepen(ST 12),and Yifeng(SJ 17),while the control group received a bilateral superficial cervical plexus block.Primary outcomes included the level of analgesia and perioperative vital signs in both groups.Additionally,pain thresholds and serum b-endorphin levels were measured before and after electroacupuncture in the EA group.Results:Complete analgesia(Level A)was attained in 86%and 76%of the patients in the EA and control groups,respectively,with no significant difference between the two groups(P=1.00).In the EA group,the mean pain threshold after receiving EA doubled(648.7(77.4)g/s vs.305.3(45.3)g/s,P<.001),and the mean serum b-endorphin level increased by approximately 13.5 pg/mL(P<.001).All patients remained hemodynamically stable throughout the surgery.Conclusion:EA,in conjunction with additional medications that stimulate five acupuncture points,LI 4,PC 6,ST 10,ST 12,and SJ 17,was well tolerated and effectively maintained a suitable level of analgesia and hemodynamic stability during total thyroidectomy.

Map activation of various brain regions using different frequencies of electroacupuncture ST36,utilizing the FosCreER strategy

Objective:Electroacupuncture(EA)is an alternative treatment option for pain.Different frequencies of EA have different painrelieving effects;however,the central mechanism is still not well understood.Methods:The Fos2A-iCreER(TRAP):Ai9 mice were divided into three groups(sham,2 Hz,and 100 Hz).The mice were intraperitoneally injected with 4-hydroxytamoxifen(4-OHT)immediately after EA at Zusanli(ST36)for 30 min to record the activated neurons.One week later,the mice were sacrificed,and the number of TRAP-treated neurons activated by EA in the thalamus,amygdala,cortex,and hypothalamus was determined.Results:In the cortex,2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1(Cg1)and primary somatosensory cortex(S1),and 2 and 100 Hz EAs did not differ from sham EA.TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex(IC)and secondary somatosensory cortex(S2)compared with those activated by 100 Hz and sham EA.In the thalamus,the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus(PV)compared with those activated by sham EA.In the ventrolateral thalamic nucleus(VL),the number of TRAPtreated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA,and sham EA showed no difference compared with 2 or 100 Hz EA.TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus(VPL)by 2 Hz EA than by 100 Hz or sham EA.Conclusions:Low-frequency EA ST36 effectively activates neurons in the Cg1,S1,S2,IC,VPL,PV,and VL.The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

Electroacupuncture with different waveforms for primary dysmenorrhea:A randomized controlled trial

Objective:To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea.Methods: This was a prospective,randomized,three-group,parallel-controlled trial.Participants with primary dysmenorrhea were randomly divided into dense-sparse wave,continuous wave,and discontinuous wave groups in a 1:1:1 ratio.Two lateral Ciliao(BL 32)points were used.All three groups started treatment 3–5 days before menstruation,once a day for six sessions per course of treatment,one course of treatment per menstrual cycle,and three menstrual cycles.The primary outcome measure was the proportion with an average visual analog scale(VAS)score reduction of≥50%from baseline for dysmenorrhea in the third menstrual cycle during treatment.The secondary outcome measures included changes in dysmenorrhea VAS scores,Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs.Results: The proportion of cases where the average VAS score for dysmenorrhea decreased by≥50%from baseline in the third menstrual cycle was not statistically significant(P>.05).Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea,there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle(P<.05).Additionally,there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture(P<.05).Conclusions: Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients.The three groups showed similar results in terms of short-and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs.Regarding achieving immediate analgesia,the dense-sparse wave group was slightly better than the other two groups.

Electroacupuncture targeting the immune system to alleviate sepsis

Sepsis is a life-threatening inflammatory syndrome with high morbidity and mortality rates.However,options for sepsis are still limited to general treatment in intensive care units(ICUs),and effective therapies that improve sepsis survival are required.Immune disturbances play a vital role in the pathology of sepsis and are associated with protracted inflammation,susceptibility to infections,and death.Therefore,many investigators have focused on the potential benefits of immunomodulation therapy for sepsis.Electroacupuncture(EA)has been practiced in clinics for many years and has shown advantages in treating infectious diseases.Over the last few decades,our understanding of the efficacy and mechanisms of EA in sepsis has undergone considerable developments.We searched the literature regarding“CNKI,Wan Fang Data,VIP Database,PubMed,and Ingenta Connect”from 2010 to 2023,using the keywords“sepsis”“septic”and“electroacupuncture”and 336 sources were searched.Finally,we included 82 studies that targeted the immune system to determine EA’s anti-inflammatory and immunomodulatory effects on sepsis.In this review,we found that EA has clinical benefits in relieving septic inflammation,improving immune function,and attenuating related multi-organ injury through several mechanisms,such as activation of the cholinergic anti-inflammatory pathway(CAP),vagaladrenal axis,inhibition of the nuclear factor Kappa-B(NF-κB)signaling pathway,signal transducers and activators of transcription(STAT)signaling pathway,and improvement of immune cell function.Therefore,EA may be a promising complementary therapy for sepsis treatment.We also expect these data will contribute to further studies on EA in sepsis.

Electroacupuncture improves myocardial fibrosis in heart failure rats by attenuating ECM collagen deposition through modulation of TGF-β1/Smads signaling pathway

Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.

Effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries

BACKGROUND The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head,maintaining shoulder joint stability.AIM To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries.METHODS We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023.Patients were grouped using the envelope method.RESULTS After treatment,the study group’s treatment effective rate was 94.90%(46/49 patients),significantly higher than that in the control group(79.17%,38/48 cases;P<0.05).Before treatment,there was no difference in Constant Murley Score(CMS)scores,shoulder mobility,or 36-Item Short Form Health Survey(SF-36)scale scores(P>0.05).Compared with those before treatment,the CMS scores(including pain,daily living ability,shoulder mobility,and muscle strength),all aspects of shoulder mobility(forward flexion,posterior extension,external rotation,internal rotation),and SF-36 scale scores(including physiological,psychological,emotional,physical,vitality,and health status)were higher in both groups after treatment and significantly higher in the study group(P<0.05).There was no difference in the occurrence of complications between the two treatment groups(P>0.05).CONCLUSION Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries,helps accelerate the recovery of shoulder function,improves the quality of life,and is highly safe.

Exploring the mechanism of electroacupuncture at different acupoints on acute colitis rats based on JAK2/STAT3/SOCS1 signaling pathway

Objective:To investigate the mechanism of JAK2/STAT3/SOCS1 signaling pathway in electroacupuncture of different acupoints on acute colitis rats.Methods:36 SPF SD rats were randomly divided into 6 groups,with 6 rats in each group.The rat model of acute colitis was prepared by enema with glacial acetic acid solution.After the model was established,electroacupuncture was given to each acupoint group,with density wave,frequency 2Hz-50 Hz,intensity 2 mA,muscle tremor as the degree 20 min/time,1 time/day,for 3 consecutive days.Observe the general condition of rats;the pathological changes of colonic mucosa in rats were observed by HE method.The contents of serum interleukin-4(IL-4)and interleukin-8(IL-8)were detected by ELISA.Western blot and RT-PCR were used to detect the expression of JAK2,STAT3,SOCS1 protein and mRNA in rat colon tissue.Results:In contrast to the normal group,the overall condition of the model group was worse,the colonic mucosa was severely damaged,even necrotic,and the ulcer surface was obvious.The content of IL-4 in serum was obviously reduced,and the content of IL-8 was obviously go up(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously go up,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously reduced(P<0.01).In contrast to the model group,the general condition of rats in each acupoint group was significantly improved,the damage and necrosis of colonic mucosa and ulcer surface were obviously alleviated,the content of IL-4 in serum was obviously go up,and the content of IL-8 was significantly decreased(P<0.01).The protein content of JAK2,STAT3 and the expression of JAK2,STAT3 mRNA in colon tissue of rats were obviously reduced,while the protein content of SOCS1 and the expression of SOCS1 mRNA were obviously go up(P<0.05,P<0.01).Comparison of different acupoint groups,the colonic mucosal injury in the Zusanli group was significantly reduced,the content of serum IL-4 was significantly increased,and the content of IL-8 was significantly decreased(P<0.05,P<0.01).The protein content and mRNA expression of JAK2 and STAT3 in colon tissue were significantly down-regulated,while the protein content and mRNA expression of SOCS1 were significantly go up(P<0.05,P<0.01).Conclusion:Electroacupuncture at each acupoint can improve the damage of colonic mucosa and reduce the inflammatory response.The therapeutic effect of Zusanli(ST36)is better than that of Tianshu(ST25),Dachangshu(BL25)and Shangjuxu(ST37).The mechanism may be related to the regulation of JAK2/STAT3/SOCS1 signaling pathway related proteins and inflammatory cytokines IL-4 and IL-8.

Preclinical Evidence and Potential Mechanisms of Electroacupuncture in Regulating Inflammatory Responses After Stroke:A Meta-analysis

[Objectives]To investigate the evidence-based effect of electroacupuncture on the post stroke inflammatory response and elucidate its potential molecular mechanisms.[Methods]Asystematic electronic search of the Medline,PubMed,and Web of Science databases was initially performed up to June 2024.The risk of bias of the included studies was evaluated using RevMan5.4 software,in accordance with the guidelines set forth in the Cochrane Handbook for Systematic Revieus.The random-effects model or fixed-effects models was employed to esti-mate the standardized mean difference(SMD).[Results]A total of 15 studies,comprising a total of 182 rats or mice,were included in this review.The pooled analysis of these trials showed a statistically significant reduction in the level of TNF-α(12 studies,SMD=-2.38,[95%CI,-2.86 to-1.90],P<0.00001,I^(2)=49),and IL-1β(11studies,SMD=-2.41,[95%CI,-3.32 to-1.50],P<0.00001,I^(2)=57).Additionally,the compiled data demonstrated a notable and statistically significant elevation in the IL-10 level(6 studies,SMD=1.56,[95%CI,0.42 to 2.70],P=0.008,I^(2)=68).[Conclusions]The findings of this systematic review and meta-analysis dem-onstrate that electroacupuncture stimulation has the potential to regulate the inflammatoryresponses after stroke.

Effect of Electroacupuncture on Infarct Size in Cerebral Ischemic Stroke:A Preclinical Meta-Analysis and Systematic Review

[Objectives]The aim of this study was to investigate the effect of electroacupuncture on infarct size in cerebral ischemic stroke.[Methods]A systematic electronic search was conducted up to June 1,2024.TTC staining was used to evaluate the infarct size.Standard mean differences(SMD)with a95%confidence interval(CI)were calculated to assess the two intervention methods.The heterogeneity of the included studies was also tested.Two analyses with subgroups were planned:intervention start time(before MCAOversus after MCAO).waveform(continuous wave versus disperse wave).[Results]Forty-one studies with a total of 502 rats or mice were included in this review.The pooled analysis of these trials showed a significant positive effect of electroacupuncture on the infarct size(SMD=-2.65,P<0.0001,Z=12.55).Subgroup analysis results indicated that electroacupuncture intervention before MCAO surgery(16 studies,SMD=-2.73,P<0.00001,Z=10.60)could more significantly reduce infarct size than that after MCAO surgery(25studies,SMD=-2.61,P<0.00001,Z=8.20).Additionally,disperse waves(31 studies,SMD=-2.46,P<0.00001,Z=11.08)were more effective in reducing infarct area than continuous waves(10 studies,SMD=-3.38,P<0.00001,Z=6.12).[Conclusions]This review provided sufficient evidence that electroacupuncture before MCAO surgery with disperse waves was more effective in reducing infarct area than after MCAO surgery and continu-ous waves.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

ADVANCES OF STUDIES ON MECHANISMS OF ELECTROACUPUNCTURE ANALGESIA

The relative reports on the effects of electroacupuncture （EA） on the nervous system and neuro- transmitters, tolerance of EA and so on in recent years are reviewed so as to reveal the analgesic mechanism of EA and provide reference for clinical researches and application of EA.

EFFECTS OF ELECTROACUPUNCTURE ON EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 IN THE RAT OF LOCAL CEREBRAL ISCHEMIA-REPERFUSION

Objective To investigate effects of electroacupuncture （EA） on expression of intercellular adhesion molecule-1 （ICAM-1） in the rat of local cerebral ischemia-reperfusion. Methods Eighty SD rats were randomly divided into a normal control group, a sham operation group, a model group and an EA treatment group, 20 rats in each group. The thread-obstruction method was used for preparation of ischemia-reperfusion model. Zea-Longa rating criteria were used for evaluation of nervous function disorder; Immunohistochemical SABC method was used for detection of ICAM-1 expression in the microvascular endothelial cell of the ischemic brain region, and ELISA method for the soluble ICAM-1 （slCAM-1） content in peripheral blood. Re. suits After cerebral ischemia-reperfusion, both ICAM-1 expression level in the microvascular endethelium cell of the ischemic brain region and slCAM-1 content in the peripheral blood significantly increased in the model group as compared with the normal group and the sham operation group （P〈0.01）; After EA treatment, the ICAM-1 expression level in the microvascular endothelial cell of the ischemic brain region and slCAM-1 content in the peripheral blood were significantly down-regulated in the EA treatment group as com- pared with the model group （P〈 0.05）. Conclusion After cerebral ischemia-reperfusion, the microvascular endothelial cell of the ischemic brain region releases ICAM-1, which induces inflammatory injury of cerebral tissues; EA treatment can decease the expression of ICAM-1, so as to prevent the brain from the injury.

PROTECTION OF ELECTROACUPUNCTURE ON HIPPOCAMPAL INJURY INDUCED BY QUINOLINIC ACID IN RATS

Objective To probe into the protective mechanism of electro-acupuncture （EA） on anti-oxygen stress in dementia-model rats. Methods A total of 30 male SD rats of cleaning grade were randomized into three groups, named sham-operation （n = 10）, model （n = 10）, model＋ EA （n = 10）. The dementia-model rat was made with hippocampal GA1 lesions by quinolinic acid （QA）. On the second day of modeling, in model＋ EA group, EA （3 Hz, 2-4 mA, continuous waves） was applied to ＂Dàzhuī＂ （大椎 GV 14） and ＂Shènshū＂ （肾俞 BL 23） for 10 min. The capability of learning and memory was evaluated by step-down test to observe the changes of nitric oxide （NO）, nitric oxide synthase （NOS） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） of the hippocampal tissues in rats separately by biochemical methods. Results EA improved learning and memory of dementia rats with hippocampal CA1 lesions induced by QA at different degrees. It significantly increased SOD activity, reduced MDA content and improved NO level and NOS activity. Conclusion EA improves significantly the learning and memory of the dementia rats due to hippocampal CA1 lesions induced by QA, which is probably relevant with the anti-oxygen stress of EA.

FORTY-EIGHT CASES OF ACUTE GOUTY ARTHRITIS TREATED COMPREHENSIVELY WITH ELECTROACUPUNCTURE AND WARMING MOXIBUSTION

Objective To probe into the effects on acute gouty arthritis treated comprehensively with electroacupuncture (EA) and warming moxibustion. Methods 70 cases were randomized into treatment group (48 cases), in which the EA+warming moxibustion was applied; and controlled group (22 cases), in which, colchicine was prescribed for oral administration. Results The statistical outcomes after 1 course treatment in treatment group: 28 cases were cured (58.33%), 18 cases improved (37.50%) and the total effective rate was 95.83%. In controlled group: 12 cases (54.55%) were cured, 8 cases improved (36.36%) and the total effective rate was 90.91%. The therapeutic effects of two groups were basically consistent, without significant different (P>0.05). But, concerning to side effect, there was no any toxic side effects in the group treated with EA+warming moxibustion, and the occurrence rate in the group treated with colchicine was 40.91%. Conclusion Electroacupuncture+warming moxibustion achieves good therapeutic effects without any side effects.

Autophagy: novel insights into therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury

Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway.This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.

Electroacupuncture promotes peripheral nerve regeneration after facial nerve crush injury and upregulates the expression of glial cell-derived neurotrophic factor

The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group(normal control, n = 21), injury group(n = 45) and electroacupuncture group(n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng(TE17), Jiache(ST6), Sibai(ST2), Dicang(ST4), Yangbai(GB14), Quanliao(SI18), and Hegu(LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Western blot assay displayed that compared with the injury group, the expression of GDNF protein levels on days 7, 14 and 21 were significantly upregulated in the electroacupuncture group. The histology with hematoxylin-eosin staining and Nissl staining of brainstem tissues containing facial neurons in the middle and lower part of the pons exhibited that on day 7 post-surgery, there were significantly fewer apoptotic neurons in the electroacupuncture group than in the injury group. By day 21, there was no significantly difference in the number of neurons between the electroacupuncture and normal groups. Taken together, these results have confirmed that electroacupuncture promotes regeneration of peripheral facial nerve injury in rabbits, inhibits neuronal apoptosis, and reduces peripheral inflammatory response, resulting in the recovery of facial muscle function. This is achieved by up-regulating the expression of GDNF and N-cadherin in central facial neurons.

Electroacupuncture in the repair of spinal cord injury:inhibiting the Notch signaling pathway and promoting neural stem cell proliferation

Electroacupuncture for the treatment of spinal cord iniury has a good dinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Daw- ley rats was clamped for 60 seconds. Dazhui （GV14） and Mingmen （GV4） acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expres- sion of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem ceils.

Effects of electroacupuncture at Zusanli(ST36) on inflammatory cytokines in a rat model of smokeinduced chronic obstructive pulmonary disease

OBJECTIVE： Improvement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease （COPD）, but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture （EA） may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD. METHODS： A COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups （control, sham, COPD, and COPD plus EA）, and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli （ST36） for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid （BALF） was used to measure levels of tumor necrosis factor-a （TNF-a）, interleukin-113 （IL-113）, and malonaldehyde （MDA）. RESULTS： Compared with the control rats, COPD rats had significant changes in lung resistance （R,） and lung compliance （C,） （both P〈0.01）, bronchi and bronchiole airway obstruction （P〈0.01）, and levels of MDA, TNF-α, and IL-1β（P〈0.01）. There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased R, and increased CL （both P〈0.05）, and reduced bronchi and bronchiole airway obstruction （P〈0.05, P〈0.01, respectively）, while levels of TNF-α, IL-1β, and MDA in BALF were lowered （P〈0.05 and P〈0.01, respectively）. However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group （P〈0.05）. CONCLUSION： EA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.

Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis

Acupuncture at Shuigou（GV26） shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26（15 Hz and 1 m A, continuous wave [biphasic pulses], for 5 minutes）. Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score. These findings confirm that electroacupuncture at GV26 promotes establishment of collateral circulation and angiogenesis, and improves neurological function.