Systematic review and Meta-analysis of brain plasticity associated with electroacupuncture in experimental ischemic stroke.

OBJECTIVE: To systematically evaluate the role of electroacupuncture in maintaining brain plasticity in ischemic stroke mediated brain damage. METHODS: We searched for all relevant trials published through Oct 7, 2022 from seven databases. Metho-dological quality was assessed using the CAMARADES Risk of Bias Tool. A Meta-analysis of comparative effects was performed using Review Manager v.5.3 software. RESULTS: A total of 101 studies involving 2148 animals were included. For most studies, primary outcomes results of the Meta-analysis indicate that EA significantly improved ischemic stroke rat's postsynaptic density thickness [Standardized Mean Difference (SMD) = 1.41, 95% confidence interval (CI) (0.59, 2.23), P = 0.0008], numerical density of synapses [SMD = 1.55, 95% CI (0.48, 2.63), P = 0.005] compared with non-EA-treated. Similarly, EA could improve parts of biomarkers of synapses, neurogenesis, angiogenesis and neurotrophin activity than the control group (P < 0.05). CONCLUSION: The existing evidence suggests EA regulating ischemic stroke may be through brain plasticity. More rigorous and high quality studies should be conducted in the future.

Regulatory role of electroacupuncture on satellite glial cell activity in the colon and dorsal root ganglion of rats with irritable bowel syndrome.

OBJECTIVE: To investigate the role of satellite glial cells in irritable bowel syndrome (IBS) and the effect of electroacupuncture (EA) at the Tianshu (ST25) and Shangjuxu (ST37) combination. METHODS: A model for visceral hypersensitivity in IBS was induced through colorectal distension (CRD) stimulation. Clean-grade male Sprague-Dawley (SD) rats were randomly divided into four groups: a normal group (NG), a model group (MG), an electroacupuncture group (EA), and a glial cell inhibitor group (FCA). Bilateral EA (2/100 Hz, 1 mA, 30 min) was administered at the Tianshu (ST25) and Shangjuxu (ST37) in week 6. Abdominal withdrawal reflex (AWR) scores were used to assess the behavioral response associated with visceral hyperalgesia, while hematoxylin-eosin staining was employed to evaluate pathological changes in the colon. The protein and mRNA levels of glial fibrillary acidic protein (GFAP) in the colon and colon-related dorsal root ganglion (DRG) were analyzed using immun-ofluorescence, immun-ohistochemistry, Western blotting, real-time polymerase chain reaction. The impact of EA on electrophysiological properties of colon-related DRG neurons was observed through whole-cell patch clamp analysis. RESULTS: EA significantly reduced the visceral pain behavior scores in rats with IBS in response to graded (20, 40, 60, 80 mm Hg) CRD stimulation. Additionally, EA downregulated the protein and mRNA expression levels of GFAP in the colon and colon-related DRG of rats with IBS. EA also regulated the resting membrane potential, rheobase and action potential of colon-related DRG neurons in rats with IBS. CONCLUSIONS: EA can regulate the excitatory properties of colon-related DRG neurons by downregulating the protein and mRNA expression of GFAP in the colon and colon-related DRG, indicating a potential neurobiological mechanism by which EA relieves visceral hypersensitivity in rats with IBS.

Electroacupuncture inhibits hippocampal oxidative stress and autophagy in sleep-deprived rats through the protein kinase B and mechanistic target of rapamycin signaling pathway.

OBJECTIVE: To investigate the effects of acupuncture on learning and memory impairment, oxidative stress and autophagy induced by sleep depriv ation in rats, and to analyze the related mechanism. METHODS: Thirty Wistar rats were randomly divided into a normal group, sleep deprivation group and acupuncture group. The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation method. The Baihui (GV20), Shenmen (HT7) and Sanyinjiao (SP6) acupoints of rats were located to give electroacupuncture (density wave, frequency 20 Hz, intensity 1 mA) to maintain the needle feeling, and to keep the needle for 15 min and continuous acupuncture for 7 d. The spatial learning and memory abilities of the rats were detected by the water maze test. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the brain were detected by an assay kit, and the autophagy related proteins light chain 3 alpha (LC3A), light chain 3 beta (LC3B) and Beclin 1 and the activation of the protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) signaling pathway in the rat's brain were detected by Western blotting. RESULTS: Compared with the normal group, the time spent in the target quadrant (P < 0.05) and the number of times entering the target quadrant (P < 0.05) in the rats of sleep deprivation group were significantly reduced, and the content of MDA was significantly increased (P < 0.01), while the activities of SOD and GPX (P < 0.01) in the brain were significantly decreased, and LC3A Ⅱ/Ⅰ, LC3B Ⅱ/Ⅰ and Beclin 1 increased significantly (P < 0.01), while p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70S6 decreased significantly (P < 0.01). Compared with the sleep deprivation group, the time spent in the target quadrant and the times of entering the target quadrant (P < 0.05) in the rats of acupuncture group after 7 d of treatment were significantly increased, Additionally, the content of MDA was significantly decreased (P < 0.05), while the activities of SOD and GPX (P < 0.05) in the brain were significantly increased. Moreover, the levels of LC3A Ⅱ/Ⅰ, LC3BⅡ/Ⅰ and Beclin 1 decreased significantly (P < 0.05), and that of p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70s6k increased significantly (P < 0.05). CONCLUSION: Acupuncture can significantly improve the learning and memory damage caused by sleep deprivation and inhibit oxidative stress and autophagy, and its effect is related to the activation of AKT/mTOR signaling.

Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.

Cardio-cerebrovascular disease (CCVD) is a serious threat to huma strategy to prevent the occurrence and development of disease by giving electroacupuncture intervention before the disease occurs. EAP has been shown in many preclinical studies to relieve ischemic symptoms and improve damage from ischemia-reperfusion, with no comprehensive review of its mechanisms in cardiovascular disease yet. In this paper, we first systematically discussed the meridian and acupoint selection law of EAP for CCVD and focused on the progress of the mechanism of action of EAP for the prevention and treatment of CCVD. As a result, in preclinical studies, AMI and MCAO models are commonly used to simulate ischemic injury in CCVD, while MIRI and CI/RI models are used to simulate reperfusion injury caused by blood flow recovery after focal tissue ischemia. According to the meridian matching rules of EAP for CCVD, PC6 in the pericardial meridian is the most commonly used acupoint in cardiovascular diseases, while GV20 in the Du meridian is the most commonly used acupoint in cerebrovascular diseases. In terms of intervention parameters, EAP intervention generally lasts for 30 min, with acupuncture depths mostly between 1.5 and 5 mm, stimulation intensities mostly at 1 mA, and commonly used frequencies being low frequencies. In terms of molecular mechanisms, the key pathways of EAP in preventing and treating cardiovascular and cerebrovascular diseases are partially similar. EAP can play a protective role in cardiovascular and cerebrovascular diseases by promoting autophagy, regulating Ca2+ overload, and promoting vascular regeneration through anti-inflammatory reactions, antioxidant stress, and anti-apoptosis. Of course, both pathways involved have their corresponding specificities. When using EAP to prevent and treat cardiovascular diseases, it involves the metabolic pathway of glutamate, while when using EAP to prevent and treat cerebrovascular diseases, it involves the homeostasis of the blood-brain barrier and the release of neurotransmitters and nutritional factors. I hope these data can provide experimental basis and reference for the clinical promotion and application of EAP in CCVD treatment.

Safety and efficacy of electro-thumbtack needle for acute mountain sickness patients: a protocol of a randomized, single-blinded, and placebo-controlled study.

BACKGROUND: Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. METHODS: This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. DISCUSSION: This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

[Pelvic floor muscle training combined with electroacupuncture for bladder dysfunction after incomplete spinal cord injury: a randomized controlled trial].

OBJECTIVE: To observe the efficacy of pelvic floor muscle training combined with electroacupuncture (EA) for bladder dysfunction after incomplete spinal cord injury (SCI). METHODS: Ninety patients with bladder dysfunction after incomplete SCI were randomly divided into an EA group (30 cases), a pelvic floor muscle training group (30 cases, 1 case dropped out), and a combined group (30 cases, 1 case dropped out). All groups received routine rehabilitation. The EA group received EA at Zhongji (CV 3), Guanyuan (CV 4), Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Shenshu (BL 23), Ciliao (BL 32), and Pangguangshu (BL 28), with continuous waves at frequency of 100 Hz, and the needles were retained for 30 min, once daily, 6 times a week for 6 weeks. The pelvic floor muscle training group underwent pelvic floor muscle training two times a day, for 6 weeks. The combined group received both EA and pelvic floor muscle training. The daily average number of urinations, daily average number of urinary leakages, urodynamic indexes (residual urine volume, maximum bladder capacity, bladder compliance, and maximum urine flow rate), and generic quality of life inventory-74 (GQOLI-74) were compared before and after treatment in each group. RESULTS: Compared before treatment, the daily average number of urinations and urinary leakages were decreased (P<0.05), residual urine volume, maximum bladder capacity, and bladder compliance were reduced (P<0.05), and maximum urine flow rate and GQOLI-74 scores were increased (P<0.05) after treatment in all groups. After treatment, the combined group showed greater differences in the daily average number of urinations, daily average number of urinary leakages, residual urine volume, maximum bladder capacity, bladder compliance, maximum urine flow rate, and GQOLI-74 score compared to the EA group and the pelvic floor muscle training group (P<0.05). There was no statistically significant differences in the changes in these indexes between the EA group and the pelvic floor muscle training group (P>0.05). CONCLUSION: Pelvic floor muscle training combined with EA can effectively alleviate urination problems in patients with bladder dysfunction after incomplete SCI, improve bladder function, and enhance patients' quality of life.

[Effects of electroacupuncture at "Jiaji" (EX-B 2) on extracellular matrix of chondrocytes and inflammatory reaction in rabbits with Modic changes of cartilage endplate].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) on extracellular matrix (ECM) of chondrocytes and inflammatory reaction in rabbits with Modic changes (MC) of cartilage endplate, and to explore the mechanism of EA in treating MC of endplate cartilage. METHODS: Eighteen male New Zealand white rabbits were randomly divided into a sham operation group, a model group and an EA group, 6 rabbits in each group. Based on the autoimmune theory, MC model was established by embedding autogenous nucleus pulposus in the rabbits of the model group and the EA group, based on autoimmunity. After successful modeling, EA was applied at bilateral "Jiaji" (EX-B 2) of L5 and L6 in the EA group, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, 20 min a time, once a day, 1-day interval was taken after continuous 6-day intervention, for 4 weeks totally. Before and after modeling, as well as before and after intervention, the comprehensive response score was observed. After modeling and intervention, magnetic resonance imaging (MRI) was used to observe the signal intensity of intervertebral disc and cartilage endplate. After intervention, the morphology of chondrocytes of cartilage endplate was observed by HE staining; the positive expression of a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS5) and Aggrecan in the cartilage endplate was detected by immunohistochemistry; the levels of inflammatory factors i.e. interleukin-1ß (1L-1ß) and tumor necrosis factor-α (TNF-α) in the cartilage endplate were detected by ELISA; the protein expression of ADAMTS5, Aggrecan, matrix metalloproteinase-13 (MMP-13), IL-1ß and TNF-α in the cartilage endplate was detected by Western blot. RESULTS: Compared with the sham operation group, in the model group, the comprehensive response score was decreased (P<0.01); L5/L6 intervertebral disc and the cancellous bones of endplate vertebral body showed low signal and unclear boundary; the chondrocytes of the cartilage endplate increased significantly, the cells were enlarged and hypertrophic, and the nuclei were wrinkled and clustered; the positive expression of ADAMTS5 as well as the levels of IL-1ß and TNF-α were increased (P<0.01), while the positive expression of Aggrecan was decreased (P<0.01) in the cartilage endplate; the protein expression of ADAMTS5, MMP-13, IL-1ß and TNF-α was increased (P<0.01), while that of Aggrecan was decreased (P<0.01) in the cartilage endplate. Compared with the model group, in the EA group, the comprehensive response score was increased (P<0.01); the signal of L5/L6 intervertebral disc and the cancellous bones of endplate vertebral body was enhanced; the chondrocytes of the cartilage endplate were reduced, the nuclei were slightly crumpled and scattered; the positive expression of ADAMTS5 as well as the levels of IL-1ß and TNF-α were decreased (P<0.05, P<0.01), while the positive expression of Aggrecan was increased (P<0.01) in the cartilage endplate; the protein expression of ADAMTS5, MMP-13, IL-1ß and TNF-α was decreased (P<0.05, P<0.01), while that of Aggrecan was increased (P<0.05) in the cartilage endplate. CONCLUSION: EA at "Jiaji" (EX-B 2) can delay the MC of cartilage endplate. The mechanism may be related to inhibiting the degradation of ECM of chondrocytes and the secretion of inflammatory factors, and repairing the degeneration of endplate cartilage.

[Effects of electroacupuncture on learning-memory function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury based on the BDNF/TrkB pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) on the expression of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, synaptophysin (SYN), and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the hippocampus of the ischemic side in rats with cerebral ischemia-reperfusion injury (CIRI), and to explore the effects and action mechanism of EA on post-CIRI learning-memory function. METHODS: Forty-eight SPF-grade male SD rats were randomly divided into a sham operation group, a model group, an EA group, and a non-acupoint group, with 12 rats in each group. The CIRI model was established in the model group, the EA group, and the non-acupoint group using the modified ZeaLonga suture method. The rats in the EA group were treated with EA at "Sishencong" (EX-HN 1) and "Baihui" (GV 20), with disperse-dense wave at frequency of 2 Hz/10 Hz and intensity of 1 mA. The rats in the non-acupoint group were treated with EA at non-meridian and non-acupoint points under the ribs bilaterally with the same parameters as the EA group. EA were conducted for 30 min each session, once daily, for 7 days. During the intervention, body weight was measured daily at a fixed time, and neurological deficits were assessed on the 1st, 3rd, and 7th days into intervention. Brain infarct volume was measured using small animal magnetic resonance imaging before and after the intervention. After the intervention, learning-memory function were evaluated using the Morris water maze. Hippocampal morphology was observed with HE staining. The positive expression of SYN in the hippocampus of the ischemic side was detected by immunohistochemistry. BDNF, TrkB, and SYN protein expressions in the hippocampus of the ischemic side were detected by Western blot. IL-1ß and IL-18 levels in the hippocampus of the ischemic side were measured by ELISA. RESULTS: From the 2nd to the 7th day into intervention, compared with the sham operation group, the body weight of rats in the model group was decreased (P<0.01); compared with the model group and the non-acupoint group, the body weight of rats in the EA group was increased (P<0.01). On the 1st day into intervention, compared with the sham operation group, neurological function scores of rats in the model group, the EA group, and the non-acupoint group were increased (P<0.01); on the 3rd and 7th days into intervention, neurological function scores of rats in the model group were higher than those in the sham operation group (P<0.01); on the 7th day, neurological function scores of rats in the EA group were lower than those in the model group and the non-acupoint group (P<0.05). Compared with the sham operation group, escape latency was prolonged (P<0.05), and the number of platform crossings was decreased (P<0.01) in the model group; compared with the model group and the non-acupoint group, escape latency was shortened (P<0.05), and the number of platform crossings was increased (P<0.01) in the EA group. Before intervention, the high signal infarcts were observed in the left ventricles of rats in the model group, the EA group, and the non-acupoint group; after intervention compared with the model group and the non-acupoint group, infarct volume in the EA group was decreased (P<0.01). Neuronal cells in the model group and the non-acupoint group were sparsely and disorderedly arranged, with deep-stained cytoplasm and shrunken nuclei; the number and arrangement of neuronal cells in the EA group were similar to the sham operation group, with less deep-stained cytoplasm and shrunken nuclei compared to the model group. Compared with the sham operation group, the positive expression of SYN, and BDNF TrkB, and SYN protein expressions in the hippocampus of the ischemic side were decreased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were increased (P<0.01) in the model group; compared with the model group and the non-acupoint group, the positive expression of SYN, and BDNF, TrkB and SYN protein expressions in the hippocampus of the ischemic side were increased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were decreased (P<0.01) in the EA group. CONCLUSION: EA at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) may improve learning-memory function in rats with CIRI by activating the BDNF/TrkB signaling pathway, reducing neuroinflammatory response, and promoting the recovery of synaptic plasticity.

Effect of electroacupuncture on the intestinal flora-short chain fatty acid metabolism axis in simple obesity rats. / ç”µé’ˆå¯¹å•çº¯æ€§è‚¥èƒ–ç—‡å¤§é¼ è‚ é“èŒç¾¤-çŸ­é“¾è„‚è‚ªé ¸ä»£è°¢è½´çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the intestinal flora-short chain fatty acids (SCFAs) metabolism axis in rats with simple obesity, so as to explore the underlying mechanism of EA in reducing obesity. METHODS: Male SD rats were randomly divided into control group, model group and EA group, with 6 rats in each group. The obesity model was established by feeding the rats with high-fat diet. Rats in the EA group were treated with EA at "Quchi" (LI11) and "Zusanli" (ST36) for 15 min, once daily for 21 consecutive days. The changes of body weight were observed every other day. H.E. staining was used to observe the pathological changes of adipose tissue and liver. The blood lipid content was detected by automatic biochemical analyzer. The diversity of intestinal flora in rat feces was analyzed by 16S rRNA high-throughput sequencing. The content of SCFAs in rat feces was detected by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS). The correlation between the relative abundance of fecal intestinal flora and the content of SCFAs in rats was analyzed by Pearson method. RESULTS: Compared with the control group, the body weight of rats, the serum total cholesterol (TC) and triglyceride (TG) were significantly increased (P<0.01) in the model group. The results of 16S rRNA sequencing showed that, at the genus level the relative abundance of Bacteroides, Butyrivibrio and Roseburia in were decreased significantly(P<0.05), while that of the Lachnospiraceae_NK4A136_group increased(P<0.05). After the intervention, compared with the model group, the body weight, serum TC and TG contents of rats in the EA group were significantly decreased (P<0.05, P<0.01)；the results of 16S rRNA sequencing showed that, the relative abundance of the Bacteroidota phylum significantly increased (P<0.01) and Firmicutes decreased (P<0.01) at the phylum level, and at the genus level the relative abundances of Bacteroides, Butyrivibrio and Roseburia significantly increased (P<0.01, P<0.05)；the contents of acetic acid and propionic acid in SCFAs significantly increased (P<0.01). H.E. staining showed an increase of the diameter of adipocytes, with obvious lipid droplets and inflammatory infiltration in the model group, which was relatively milder in the EA group. PCoA analysis showed that there were significant differences in the structure of intestinal flora between the control group and the model group, as well as the model group and the EA group. At the phylum level, the relative abundance of Bacteroidota was positively correlated with acetic acid and propionic acid contents, with that of Firmicutes negatively correlated with acetic acid and propionic acid contents (P<0.001). At the genus level, the relative abundances of Bacteroides, Streptococcus and Butyricimonas were positively correlated with acetic acid content (P<0.01, P<0.05), and the relative abundances of Bacteroides, Streptococcus and Roseburia were positively correlated with propionic acid content (P<0.001, (P<0.05). CONCLUSIONS: EA can improve the disorder of lipid metabolism in obese rats by improving the disorder of intestinal flora-SCFAs metabolic axis, thus playing a role in inhibiting obesity.

Electroacupuncture alleviates neuropathic pain by regulating hippocampal SP/NK1R/ARRB1 pathway. / 电针调控海马SP/NK1R/ARRB1é€šè·¯ç¼“è§£å¤§é¼ ç¥žç»ç— ç†æ€§ç–¼ç—›çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on pain, anxiety like behavior, and substance P(SP) /neurokinin-1 receptor (NK1R) /ß -arrestin 1(ARRB1) pathway related protein expression in hippocampus of chronic constriction injury (CCI) rats, so as to explore its mechanisms underlying improvement of neuropathic pain. METHODS: Twenty-seven male SD rats were randomly divided into sham operation, model and EA groups, with 9 rats in each group. The CCI model was established by ligature of the left sciatic nerve. On the 8th day following modeling, EA (2 Hz, 0.5-1.5 mA) was applied to the left "Huantiao" (GB34) and "Yanglingquan" (GB34) for 30 min, once every other day for 13 times. Mechanical paw withdrawal threshold (MWT), thermal paw withdrawal threshold (TWL) and difference of the weight distribution of the hind limbs were detected before operation and at the 5th, 9th, 17th, 25th and 33rd days after operation. Open field test was used to evaluate the anxiety-like behavior of rats. The content of SP in hippocampus was determined by ELISA. The protein expression of NK1R and ARRB1 in hippocampus was detected by Western blot. RESULTS: Compared with the sham operation group, the MWT and TWL of the left hind limb at the 5th, 9th, 17th, 25th and 33rd days after operation, the time of entering the central area and the total distance of movement, and the content of SP in the hippocampus were significantly decreased (P<0.001, P<0.01), while the difference of the weight distribution of the hind limbs at the 5th, 9th, 17th, 25th and 33rd days after operation and the protein expression of NK1R and ARRB1 were significantly increased (P<0.001, P<0.05) in the model group. After EA intervention, the MWT and TWL of the left hind limb, the time of entering the central area and the total moving distance, and the expression of SP in the hippocampus were significantly increased (P<0.01, P<0.001, P<0.05), while the difference in the weight distribution of the hind limbs was significantly reduced, and the expression of NK1R and ARRB1 protein in the hippocampus were significantly decreased (P<0.001, P<0.05) in the EA group. CONCLUSIONS: EA can effectively improve the pain and anxiety behaviors in CCI rats, and reverse the abnormal expression of SP, NK1R and ARRB1 proteins in the hippocampus, which may be related to its effects in regulating the SP/NK1R/ARRB1 pathway in the hippocampus.

Electroacupuncture promotes angiogenesis by regulating miR-142-5p and activating ADAMTS1/PI3K/AKT pathway in ischemic stroke rats. / 电针调控miR-142-5p和ADAMTS1/PI3K/AKTé€šè·¯ä¿ƒè¿›ç¼ºè¡€æ€§è„‘å’ä¸­å¤§é¼ è¡€ç®¡æ–°ç”Ÿçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke. METHODS: This study was divided into two parts. The first part of the experiment：SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively；HE staining was used to observe the cortical pathological changes；immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment：The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot. RESULTS: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased (P<0.01)；the volume of cerebral infarction in the model group was significantly increased (P<0.01)；the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased；the cerebral microvascular density was significantly increased (P<0.01)；the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased (P<0.01, P<0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated (P<0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated (P<0.01, P<0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased (P<0.01), the volume of cerebral infarction was significantly decreased (P<0.01)；the degree of brain edema and neuronal necrosis were alleviated；the cerebral microvascular density was significantly increased (P<0.01)；the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased (P<0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased (P<0.01, P<0.05), while the mRNA and protein expression of ADAMTS1 were decreased (P<0.05, P<0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased(P<0.05), while the mRNA and protein expression of ADAMTS1 were increased (P<0.01, P<0.05). CONCLUSIONS: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.

Effect of electroacupuncture on expression of autophagy-related proteins in nucleus pulposus of cervical spondylosis rabbits. / ç”µé’ˆå¯¹é¢ˆæ¤Žç— å®¶å ”é«“æ ¸ç»†èƒžè‡ªå™¬ç›¸å ³è›‹ç™½è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the morphological changes of intervertebral disc tissues, apoptosis of nucleus pulposus cells, and the protein expression of Unc-51 like autophagy-activated kinase 1 (ULK1), homologous series of yeast Atg6 (Beclin1), and light chain protease complication 3 type (LC3) in nucleus pulposus tissue of cervical spondylosis rabbits, so as to explore the role of cellular autophagy in EA treatment of cervical spondylosis. METHODS: A total of 24 New Zealand white rabbits were randomly divided into blank, model and EA groups, with 8 rabbits in each group. In the EA group, both sides of the cervical (C)3-C6 "Jiaji" (EX-B2) were stimulated by EA (2 Hz/100 Hz, 1 mA) for 25 min, once daily for 5 days in a course, with a 2-day interval between courses, totaling 4 treatment courses. X-ray was used to assess cervical spine radiographic changes and evaluate radiographic scores；transmission electron microscopy was used to observe ultrastructural changes in nucleus pulposus cells；HE staining was used to observe morphological changes of intervertebral disc tissues and conduct pathological scoring；TUNEL staining was used to observe apoptosis rate of nucleus pulposus cells；Western blot was performed to detect protein expression levels of ULK1, Beclin1, and LC3 in nucleus pulposus tissue. RESULTS: Compared with the blank group, rabbits in the model group showed significantly higher cervical spine radiographic scores (P<0.01), higher pathological scores of intervertebral disc tissues (P<0.05), increased apoptosis rate of nucleus pulposus cells (P<0.01), and decreased expression levels of ULK1, Beclin1, and LC3Ⅱ proteins in nucleus pulposus tissue (P<0.05). Compared with the model group, the EA group showed significantly lower pathological scores of intervertebral discs (P<0.05), lower apoptosis rate of nucleus pulposus cells (P<0.01), and higher protein expression levels of ULK1, Beclin1, and LC3Ⅱ in nucleus pulposus tissue (P<0.01). Rabbits in the blank control group exhibited generally normal organelle structures in nucleus pulposus tissues with few autophagic vacuoles, indicative of early stages of autophagy；while those in the model group showed disrupted organelle structures with cytoplasmic condensation and those in the EA group exhibited autophagosomes with double-membrane structures in nucleus pulposus tissues. CONCLUSIONS: EA promotes the expression of ULK1, Beclin1, and LC3Ⅱ proteins in nucleus pulposus tissues, reduces apoptosis of nucleus pulposus cells, and improves intervertebral disc degeneration.

Exploration of the mechanism underlying the therapeutic effect of electroacupuncture at chengshan acupoint on post-hemorrhoidectomy anal pain: Insights from the mAChRs/IP3-Ca2+-CaM signaling pathway.

OBJECTIVE: In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. METHODS: Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. RESULTS: The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. INTERPRETATION: These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management.

Electroacupuncture inhibited carrageenan-induced pain aversion by activating GABAergic neurons in the ACC.

Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

Transcriptome analysis of rats with chronic unpredictable mild stress treated with electroacupuncture.

BACKGROUND: Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Electroacupuncture (EA), a nonpharmacologic therapy, holds great promise for alleviating depressive symptoms. In this study, RNA sequencing (RNA-Seq) was used to identify genome-wide alterations in the hippocampus of rats after chronic unpredictable mild stress (CUMS) and EA treatments to further elucidate the mechanism by which EA ameliorates depression to provide a basis for the clinical application of EA in stress-related diseases. METHODS: The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to investigate the ability of EA at Baihui (GV20) and Taichong acupoints (LR3) to improve depression-like behavior in rats subjected to CUMS. Subsequently, RNA-Seq analysis revealed transcriptomic profiles of the hippocampus of rats subjected to CUMS in which EA ameliorated depressive behavior. Finally, the expression profiles of major differentially expressed genes were tested by real-time quantitative polymerase chain reaction (qRT-PCR) to determine the accuracy of the RNA-Seq results. RESULTS: Rats subjected to CUMS exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT (p < .001), decreased time in the central area of the OFT (p < .001), and increased immobility in the FST (p < .01). Importantly, rats subjected to CUMS and treated with EA showed increased sucrose consumption (p < .001), increased time spent in the central area of the OFT (p < .001) and decreased immobility in the FST (p < .01). Sixty-three genes that were differentially expressed following CUMS were altered by EA; most of these were associated with immune pathways. Compared with those in the control group, the expression levels of Colla2 (p < .001), Col3a1 (p < .001), Psmb9 (p < .01), and Tap1 (p < .01) in the hippocampus of rats subjected to CUMS were lower. The changes in the expression of these genes were reversed by EA treatment. CONCLUSION: EA at GV20 and LR3 attenuated CUMS-induced depression-like behaviors by regulating the expression of specific genes such as Colla2, Col3a1, Psmb9, and Tap1.

Specific mode electroacupuncture stimulation opens the blood-brain barrier of the infarcted border zone in rats during MCAO/R recovery via modulation of tight junction protein expression by VEGFA and NF-κB.

The blood-brain barrier (BBB) strictly limits the entry of most exogenous therapeutic drugs into the brain, which brings great challenges to the drug treatment of refractory central diseases, including the treatment of ischemic stroke. Our previous studies have shown that specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, but with the mechanisms largely unknown. This study explored whether SMES opens the BBB in the infarcted border zone of rats during middle cerebral artery occlusion/reperfusion recovery, and whether this is related to p65 or vascular endothelial growth factor A (VEGFA) modulation of tight junction protein expression through in vivo and in vitro studies. Evans blue, FITC-dextran, mouse-derived nerve growth factor (NGF), and transendothelial electrical resistance values were used to evaluate the permeability of the BBB. Additionally, microvascular endothelial cells and astrocytes were utilized for in vitro study. Immunofluorescence, immunohistochemistry, western blot, and ELISA were employed to assess related protein expression. SMES significantly increased vascular permeability for Evans blue and NGF in the infarcted border zone, and increased the expression of VEGFA by activating p-p65, thereby reducing the expression of tight junction proteins Occludin and ZO-1. Correspondingly, oxygen glucose deprivation/reoxygenation activated p-p65 in and induced VEGFA secretion from astrocytes in vitro. Their conditioned medium reduced the expression of Occludin in bEnd.3 cells and increased the permeability of FITC-dextran. The mechanism of SMES opening infarcted border zone BBB is partly related to its actions on p65, VEGFA, and tight junction proteins.

Clinical Efficacy of Electroacupuncture at Sacral Four Points Combined with Moxibustion at Abdominal Three Points for Treating Post-Stroke Urinary Incontinence: Observations on Urodynamics, Quality of Life, and Safety.

BACKGROUND: Urinary incontinence is a common complication following a stroke. No specific drugs are available in Western medicine, and surgical treatment is highly traumatic, limiting its clinical application. This study aimed to observe the clinical efficacy of electroacupuncture at the "Sacral Four Points" combined with moxibustion at the "Abdominal Three Points" on post-stroke urinary incontinence, exploring its impact on urodynamics and quality of life. METHODS: Patients with post-stroke urinary incontinence treated at our Hospital from January 2021 to December 2023 were recruited. The study included 117 patients: 57 in the electroacupuncture group and 60 in the combined group. Urodynamic parameters were measured, and scores from the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Incontinence Quality of Life Questionnaire (I-QOL) were recorded before, and after the first and third courses of treatment. Clinical efficacy and adverse reactions were evaluated post-treatment. RESULTS: The study found no significant differences in clinical characteristics between the groups (p > 0.05), providing a baseline for comparison. Both groups showed substantial decreases in leakage volume after one course of treatment (p < 0.05), with a reduction in the ICIQ-UI SF score (p < 0.05) and an increase in the I-QOL score (p < 0.05). After three courses of treatment, the leakage volume of patients in both groups significantly decreased (p < 0.05), the ICIQ-UI SF score decreased (p < 0.05), and the I-QOL score increased (p < 0.05). The combined group showed a lower leakage volume compared to the electroacupuncture group (p < 0.05), with lower ICIQ-UI SF scores (p = 0.027) and higher I-QOL scores (p = 0.048). Importantly, the total effective rate was significantly higher in the combined group (88.33% vs 64.91%, p = 0.037), demonstrating the safety and efficacy of the treatment. CONCLUSIONS: Electroacupuncture at the "Sacral Four Points" combined with moxibustion at the "Abdominal Three Points" improves the clinical symptoms and enhances the quality of life for patients with post-stroke urinary incontinence, showing superior results compared to electroacupuncture alone.

Neurophysiological Basis of Electroacupuncture Stimulation in the Treatment of Cardiovascular-Related Diseases: Vagal Interoceptive Loops.

PURPOSE: The vagal sensory nerve (VSN) is an essential interoceptive pathway that is connected to every level of the body. Its intricate genetic coding provides sustenance for physiological processes, including controlling blood pressure and respiration. Electroacupuncture (EA) is a proven surface stimulation therapy that can regulate vagal nerve activity, which can effectively prevent cardiovascular diseases. A growing number of studies have concentrated on the mapping of VSN codes, but little is known, and the physiological background of how EA influences interoceptive has not been fully explored. METHOD: Here, we incorporate the hypothesized interaction among EA targets, VSNs, and the heart. This offers suggestions for using a versatile and focused EA strategy to modify vagal interoceptive awareness to enhance cardiovascular conditions. We first clarified the major role of vagal nerve in the control of cardiac activity. Additionally, we clarified the multidimensional coding pattern in the VSNs, revealing that the targeted control of multimodal interoceptive is the functional basis of the synchronization of cardiovascular system. FINDING: We propose a strategy in which EA of the VSNs is employed to activate the interoceptive loop and reduce the risk of cardiovascular disease.

Electroacupuncture reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia.

Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.