Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain.

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days. Results demonstrated that EA effectively attenuated CCI-induced pain hypersensitivity and mitigated neuron damage and loss in the spinal cord of NP rats. Moreover, EA reversed the oxidative stress-mediated spinal ferroptosis phenotype by upregulating reduced expression of xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) and superoxide dismutase (SOD) levels, and downregulating increased expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), malondialdehyde levels and iron overload. Furthermore, EA increased the immunofluorescence co-staining of GPX4 in neurons cells of the spinal cord of CCI rats. Mechanistic analysis unveiled that the inhibition of antioxidant pathway of Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal ferroptosis in NP rats while marginally diminishing its analgesic effect. These findings suggest that EA treatment at acupoints ST36 and GV20 may protect against NP by inhibiting neuronal ferroptosis in the spinal cord, partially through the activation of Nrf2 signalling.

Effect and safety of electroacupuncture on weight loss in obese patients with pre-diabetes: study protocol of a randomised controlled trial.

INTRODUCTION: Obesity has been identified as a significant risk factor for several chronic conditions, including diabetes, tumours and cardiovascular disease, and has been associated with increased mortality rates. Despite the well-established clinical practice of electroacupuncture (EA) as a potential treatment option for obesity, its efficacy remains questionable, primarily due to the paucity of empirical evidence supporting its therapeutic benefits. METHODS AND ANALYSIS: The present study aims to investigate the efficacy and safety of EA for weight loss in obese individuals with pre-diabetes, using a randomised, placebo-controlled clinical trial design. A total of 256 eligible patients will be randomly assigned to one of two groups: EA (comprising EA treatment with health education) or superficial acupuncture (SA) (comprising SA treatment with health education). The intervention will be administered three times per week for the initial 12 weeks, two times per week for the subsequent 8 weeks and one time per week for the final 4 weeks, with a 24-week follow-up period. The primary outcome measure will be the percentage of patients who achieve a reduction of 10% or more in their body weight at week 24. Secondary outcome measures will include changes in body weight and body mass index, blood test results, data collected by the body composition analyser, size of adipose tissue scanned by MRI of the abdomen and the Impact of Weight on Quality of Life, the 21-item Three-Factor Eating Questionnaire-Revised and the Food Craving Questionnaire-Trait. The Treatment Emergent Symptom Scale will be employed to monitor every adverse reaction from baseline to follow-up. ETHICS AND DISSEMINATION: This trial has received ethical clearance from the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine under the registration number 2021SHL-KY-74. All participants will provide their written informed consent prior to their enrolment. The findings of this investigation will be disseminated through peer-reviewed publications and scholarly conferences. TRIAL REGISTRATION NUMBER: NCT05237089.

Clinical efficacy of acupuncture in treating postoperative gastrointestinal dysfunction of colorectal cancer, a systematic review and Meta analysis. / é’ˆåˆºæ²»ç–—ç»“ç›´è‚ ç™Œæœ¯åŽèƒƒè‚ åŠŸèƒ½éšœç¢ç–—æ•ˆçš„ 系统评价和Meta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in the treatment of postoperative gastrointestinal dysfunction(POGD) of colorectal cancer. METHODS: Randomized controlled trials of acupuncture in the treatment of POGD were retrieved from 7 databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Chinese Journal Service Platform, WanFang Data Knowledge Service Platform, and China Biology Medicine disc. The search period ranged from the inception of the databases to November 10th, 2022. The quality of the included literature was assessed using the Cochrane bias risk assessment tool and the modified Jadad scale. Meta analysis was conducted using RevMan 5.4. Regression analysis and bias risk analysis were performed using Stata 16.0. Trial sequential analysis was conducted using TSA 0.9 software. RESULTS: A total of 27 randomized controlled trials involving 2 629 patients were included. Intervention measures included manual acupuncture, electroacupuncture, transcutaneous acupoint electrical stimulation, warm acupuncture, and thumb-tack needle. The results showed that acupuncture treatment significantly reduced time to tolerance of liquid diet after surgery (MD=-13.70, 95% CI=ï¼»-17.94, -9.46ï¼½, P<0.000 01), time to first defecation (MD=-18.20, 95% CI=ï¼»-22.62, -13.78ï¼½, P<0.000 01), time to first flatus (MD=-16.31, 95% CI=ï¼»-20.32, -12.31ï¼½, P<0.000 01), time to bowel sounds recovery (MD=-11.91, 95% CI=ï¼»-14.01, -9.81ï¼½, P<0.000 01), and length of hospital stay (MD=-1.49, 95% CI=ï¼»-2.27, -0.70ï¼½, P=0.000 2). Regression analysis indicated that cancer type, study quality and number of acupuncture were the main sources of heterogeneity. Bias analysis suggested potential publication bias risks. Trial sequential analysis indicated that the required number of cases had been met and the conclusion was reliable. CONCLUSIONS: Acupuncture is an effective intervention for promoting gastrointestinal recovery in patients undergoing colorectal cancer surgery. Further large-sample and well-designed clinical trials are still needed to compare different acupuncture techniques.

Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

BACKGROUND: Mild traumatic brain injury (mTBI) is a common neurological trauma that can lead to cognitive impairment. The sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) pathway has been reported to have neuroprotective effects in rats with craniocerebral injury. We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI, focusing on the SIRT-1/PGC-1α/mitochondrial pathway. METHODS: We included forty 6-week-old male Sprague-Dawley rats in this study. Rats were randomly divided into four groups: controlled cortical impactor (CCI, n = 10), sham operation (sham, n = 10), electroacupuncture-treated CCI (CCI+EA, n = 10), and electroacupuncture-treated sham (sham+EA, n = 10) group. Randomization was performed by assigning a random number to each rat and using a random number table. The mTBI rat model was established using a controllable cortical impactor. Electroacupuncture therapy was performed on the back of rats, by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment. We evaluated spatial learning and memory functions with the Morris water maze test. We performed quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, adenosine triphosphate (ATP) determination, and mitochondrial respiratory chain complex I (MRCC I) determination on rat hippocampal tissue. We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays, and compared differences between groups using bilateral Student's t -tests. RESULTS: Compared with the sham group, SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group ( P <0.01). Although this expression was upregulated following electroacupuncture, it did not reach the levels observed in the sham group ( P <0.05). Compared with the sham group, MRCC I and ATP levels in the CCI group were significantly reduced, and increased after electroacupuncture ( P <0.01). In the Morris water maze, electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms ( P <0.05). CONCLUSION: Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke.

AIMS: We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke. METHODS: We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT-PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA. RESULTS: EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post-MCAO. EA also downregulated the expression of pro-inflammatory cytokines, including Tnf-α, Il-6, Il-1ß, and Ccl-2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect. CONCLUSION: EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Electroacupuncture Alleviates Pain by Suppressing P2Y12R-Dependent Microglial Activation in Monoarthritic Rats.

Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund's adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.

Electroacupuncture Enhances the Functional Connectivity of Limbic System to Neocortex in the 5xFAD Mouse Model of Alzheimer's Disease.

Our previous study revealed that acupuncture may exhibit therapeutic effects on Alzheimer's disease (AD) through the activation of metabolism in memory-related brain regions. However, the underlying functional mechanism remains poorly understood and warrants further investigation. In this study, we used resting-state functional magnetic resonance imaging (rsfMRI) to explore the potential effect of electroacupuncture (EA) on the 5xFAD mouse model of AD. We found that the EA group exhibited significant improvements in the number of platforms crossed and the time spent in the target quadrant when compared with the Model group (p < 0.05). The functional connectivity (FC) of left hippocampus (Hip) was enhanced significantly among 12 regions of interest (ROIs) in the EA group (p < 0.05). Based on the left Hip as the seed point, the rsfMRI analysis of the entire brain revealed increased FC between the limbic system and the neocortex in the 5xFAD mice after EA treatment. Additionally, the expression of amyloid-ß(Aß) protein and deposition in the Hip showed a downward trend in the EA group compared to the Model group (p < 0.05). In conclusion, our findings indicate that EA treatment can improve the learning and memory abilities and inhibit the expression of Aß protein and deposition of 5xFAD mice. This improvement may be attributed to the enhancement of the resting-state functional activity and connectivity within the limbic-neocortical neural circuit, which are crucial for cognition, motor function, as well as spatial learning and memory abilities in AD mice.

Effects of electroacupuncture on obesity: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis evaluated the efficacy of electroacupuncture for the treatment of obesity. METHODS: We searched 8 electronic databases for articles published between 2005 and 2021, including only randomized controlled trials (RCTs) in the review. The intervention groups received either electroacupuncture alone or electroacupuncture with standard care, whereas the control groups received sham electroacupuncture, standard care, or no treatment. The primary outcome was the body mass index (BMI), and the secondary outcomes were the body weight (BW), waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat mass, body fat percentage, and adverse effects. Continuous outcome data are presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: This systematic review and meta-analysis included 13 RCTs involving 779 participants. Results revealed that the BMI (MD: -0.98; 95% CI: -1.35 to -0.61), BW (MD: -1.89; 95% CI: -2.97 to -0.80), WC (MD: -2.67; 95% CI: -4.52 to -0.82), and WHR (MD: -0.03; 95% CI: -0.06 to -0.01) were significantly improved in the intervention groups compared with those in the control groups. Adverse effects were reported in 5 studies. The most commonly used acupoint in the abdomen was ST25, whereas the most commonly used acupoints in other regions were ST36 and SP6 for the treatment of obesity. ST25 was the most commonly used acupoint connected by electroacupuncture. CONCLUSION: This systematic review and meta-analysis suggested that electroacupuncture is an effective and safe therapy for simple obesity. To increase the reliability of this study, further detailed, long-term studies should be conducted on the effects of electroacupuncture on obesity.

Limbic system plasticity after electroacupuncture intervention in knee osteoarthritis rats.

Knee osteoarthritis (KOA) is characterized by debilitating pain. Electroacupuncture (EA), a traditional Chinese medical therapy, has shown promise in KOA pain management. This study investigated the therapeutic potential of EA in KOA and its impact on limbic system neural plasticity. Sixteen rats were randomly assigned into two groups: EA group and sham-EA group. EA or sham-EA interventions were administered at acupoints ST32 (Futu) and ST36 (Zusanli) for three weeks. Post-intervention resting-state fMRI was scanned, assessing parameters including Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and nodal characterizations of network within limbic system. The results showed that EA was strategically directed towards the limbic system, resulting in discernible alterations in neural activity, FC, and network characteristics. Our findings demonstrate that EA had a significant impact on the limbic system neural plasticity in rats with KOA, presenting a novel nonpharmacological approach for KOA treatment.

Electroacupuncture stimulation to modulate neural oscillations in promoting neurological rehabilitation.

Electroacupuncture (EA) stimulation is a modern neuromodulation technique that integrates traditional Chinese acupuncture therapy with contemporary electrical stimulation. It involves the application of electrical currents to specific acupoints on the body following acupuncture. EA has been widely used in the treatment of various neurological disorders, including epilepsy, stroke, Parkinson's disease, and Alzheimer's disease. Recent research suggests that EA stimulation may modulate neural oscillations, correcting abnormal brain electrical activity, therefore promoting brain function and aiding in neurological rehabilitation. This paper conducted a comprehensive search in databases such as PubMed, Web of Science, and CNKI using keywords like "electroacupuncture," "neural oscillations," and "neurorehabilitation", covering the period from year 1980 to 2023. We provide a detailed overview of how electroacupuncture stimulation modulates neural oscillations, including maintaining neural activity homeostasis, influencing neurotransmitter release, improving cerebral hemodynamics, and enhancing specific neural functional networks. The paper also discusses the current state of research, limitations of electroacupuncture-induced neural oscillation techniques, and explores prospects for their combined application, aiming to offer broader insights for both basic and clinical research.

Electroacupuncture ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment through suppressing oxidative stress and neuroinflammation in rats.

BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Electroacupuncture protects against the striatum of ischemia stroke by inhibiting the HMGB1/RAGE/p-JNK signaling pathways.

The striatum (Str) is injured 20 min after permanent ischemic stroke, leading to neurological deficits. Here, we aimed to explore the effect of electroacupuncture (EA) on ischemic stroke and elucidate the possible underlying mechanism. Rat permanent middle cerebral artery occlusion (pMCAO) model, EA treatment, sham-EA (SEA) treatment, beam-balance test, hematoxylin and eosin (HE) staining, Nissl staining, immunofluorescence staining, and Western blot were used to investigate the role of EA in pMCAO. The results showed that balance ability and motor coordination were obviously injured after pMCAO. EA improved balance ability and motor coordination in pMCAO rats. EA reduced striatal injury by reducing the expression of high-mobility group box 1(HMGB1)/receptor for advanced glycation end products (RAGE)/phosphorylated C-Jun N-terminal kinase (p-JNK), whereas SEA did not. Thus, EA plays a neuroprotective role during pMCAO injury, which may be related to the inhibition of HMGB1/RAGE/p-JNK expression.

Electroacupuncture combined with wet compress formula ameliorates upper limb dysfunction associated with stroke: A retrospective analysis of 126 cases.

OBJECTIVES: Upper limb motor dysfunction (ULMD) is one of the most common complications of ischemic stroke (IS). Electroacupuncture (EA) is a noninvasive procedure that has the potential to manage symptoms associated with IS. To improve the treatment effects of EA, our hospital performed combined treating strategy against ULMD by subjecting IS patients to both EA and external application of wet compress formula (WCF). In the current analysis, the potential improving effects of the combined treatment against ULMD were evaluated. MATERIALS AND METHODS: 126 patients with ULMD induced by IS handled with normal rehabilitation treatment, EA treatment alone, and EA combined with WCF respectively were enrolled in the current analysis. The clinicopathological information and changes in motor function assessment scales, including Visual analogue (VAS), Fugl-Meyer assessment-upper extremity (FMA-UA), and Modified Barthel index (MBI) scales were collected and the difference between different treating strategies was assessed. RESULTS: All the treating strategies improved the values of VAS, FMA-UA, and MBI scales, with combined treating strategy showing the strongest improving effects, and traditional rehabilitation strategy showing the weakest effects. Moreover, the assessment of hand and wrist motor function by FMA-UE also showed that the combined treatment strategy has significantly stronger improving effects against ULMD compared with other strategies. CONCLUSIONS: The current analysis showed that the use of external application of WCF could substantially increase the treating effects of EA on ULMD induced by IS without severe side effects, which could guide the future clinical management of motor dysfunction.

Characteristics of Electroacupuncture Preconditioning and Treatment on Regulation of the Brain Transcriptome in Rats with Ischemic Stroke.

BACKGROUND: Accumulating evidence suggests that acupuncture may serve as a potent strategy to mitigate the deleterious effects of ischemic stroke on neural tissue. The present investigation delineated the neuroprotective potential of electroacupuncture (EA) administered pre-and post-stroke, with a focus on determining the commonalities and disparities between these two therapeutic approaches in ameliorating ischemic stroke-induced brain injury. The ultimate objective is to inform optimal timing for acupuncture intervention in the clinical management and prevention of stroke. METHODS: The extent of cerebral infarction was quantified with 2,3,5-triphenyltetrazolium chloride staining. The integrity of the blood-brain barrier was assessed by evaluating the extravasation of Evans blue (EB) dye, while neurological function was appraised using the Longa neurological scoring system. RNA sequencing was employed to examine the transcriptomic landscape of ischemic brain tissue, with subsequent bioinformatics annotation of the sequencing data facilitated by Metascape. RESULTS: (1) A notable decrease in the ischemic infarct volume was observed in both the EA-preconditioned plus middle cerebral artery occlusion (MCAO), EA-preconditioned plus middle cerebral artery occlusion (EAM) and MCAO plus EA-treated (MEA) groups, compared to the MCAO group. Furthermore, the decreased leakage of EB and reduction in neurological function impairment scores were evident in the EAM and MEA groups compared with the MCAO group. (2) Relative to the Sham group, the MCAO group exhibited a total of 4798 differentially expressed genes (DEGs), with 67.84% demonstrating an expression fold change (FC) greater than 1.5, and 34.16% exceeding a FC of 2. The EAM and MEA groups displayed 4020 and 1956 DEGs, respectively, compared to the MCAO group. In both groups, more than 55% of DEGs showed an expression FC surpassing 1.5, whereas only approximately 10% exhibited a change greater than 2-fold. Remarkably, EA preconditioning and EA treatment resulted in the reversal of 18.72% and 28.91% of DEGs, respectively, in the MCAO group. (3) The DEGs upregulated in response to ischemic stroke were predominantly implicated in immune inflammatory processes and cellular apoptosis, whereas the downregulated DEGs were associated with neurogenesis and neuronal signal transduction. The MEA-induced upregulated DEGs were primarily involved in neural transmission and metabolic processes, whereas the downregulated DEGs were linked to excessive inflammatory responses to physical and chemical stimuli, as well as cell matrix adhesion chemotaxis. In the context of EAM, the upregulated DEGs were chiefly related to protein biosynthesis, and energy and metabolic processes, whereas the downregulated genes were connected to gene transcriptional activity, synaptic function, and neuronal architecture. CONCLUSIONS: Both preconditioning and post-event treatment with acupuncture demonstrated efficacy in mitigating pathological damage to brain tissue in a rat model of ischemic stroke, albeit with some divergences in their gene targets. The integration of EA preconditioning and treatment may potentially confer enhanced neuroprotection in the clinical management of stroke patients.

Effects of electroacupuncture on imaging and behavior in rats with ischemic stroke through miR-212-5p.

BACKGROUND: Ischemic stroke is a serious disease leading to significant disability in humans worldwide. Increasing evidence suggests that some microRNAs (miRNAs) participate in the pathophysiology of ischemic stroke. A key role for MiR-212 has been found in neuronal function and synaptic plasticity. Ischemic stroke can be effectively treated with electroacupuncture (EA); however, there is a lack of understanding of the relevant mechanisms. In this study, we employed behavioral test and resting-state functional magnetic resonance imaging (rs-fMRI) to detect behavioral and brain function alterations in rats suffering from ischemic stroke. The efficacy of EA therapy and miR-212-5p's role in this process were also evaluated. METHODS AND RESULTS: Forty rats were randomly divided into the following groups: Sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EA, MCAO/R + EA + antagomir-negative control and MCAO/R + EA + antagomir-212-5p groups. Behavioral changes were assessed by Catwalk gait analysis prior to and after modeling. Rs-fMRI was performed at one week after EA treatment, amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated to reveal neural activity. Furthermore, neuronal apoptosis in the ischemic penumbra was analyzed using a TUNEL assay. Treatment with EA significantly improved the performance of rats in the behavioral test. The motor and cognition-related brain regions showed decreased ALFF and ReHo following focal cerebral ischemia-reperfusion, and EA treatment could reactivate these brain regions. Moreover, EA treatment significantly decreased MCAO/R-induced cell death. However, the transfection of antagomir-212-5p attenuated the therapeutic effect of EA. CONCLUSIONS: In conclusion, the results suggested that EA improved the behavioral and imaging outcomes of ischemic stroke through miR-212-5p.

Effects of electroacupuncture preconditioning on microglial cells and serum inflammatory factors in the early stage of ischemic stroke. / ç”µé’ˆé¢„å¤„ç†å¯¹ç¼ºè¡€æ€§ä¸­é£Žå°é¼ æ—©æœŸå°èƒ¶è´¨ç»†èƒžåŠè¡€æ¸ ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To investigate the effects on the motor function, cortex blood flow perfusion, microglial cells, and the contents of serum inflammatory factors, i.e. interleukin-1ß (IL-1ß), transforming growth factor-ß (TGF-ß), and interleukin-10 (IL-10) after electroacupuncture (EA) preconditioning at "Baihui" (GV20) and "Dazhui" (GV14) in the mice with ischemic stroke, so as to explore the mechanism of EA preconditioning for improving motor function after ischemic stroke. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, and EA preconditioning group (EA group), with 15 mice in each group. A photothrombotic method was used to induce the model of unilateral ischemic stroke and motor impairment. The mice in the EA group received EA preconditioning, 20 min each time, once daily for 7 consecutive days before modeling. The motor function of mice was evaluated by the grid-walking test and cylinder test before and after modeling. Laser speckle blood flow video monitoring system was employed to assess the cerebral blood flow perfusion in the primary motor cortex of mice. The contents of IL-1ß, TGF-ß, and IL-10 in the serum were measured by ELISA, and the expressions of microglial cell and M2 subtype cell marker in the primary motor cortex were detected using immunofluorescence staining. RESULTS: After modeling, compared with the sham-operation group, the grid error rate and the dragging rate of the affected limb were increased (P<0.01)；the utilization rate of the affected limb and percentage of the blood perfusion in the affected cortex to healthy side were decreased (P<0.01)；the contents of serum IL-1ß, TGF-ß, and IL-10 were increased (P<0.01, P<0.05)；and the microglia in the primary motor cortex on the affected side showed ameboid, the fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA1) and CD206 was increased (P<0.01) in the model group. In the EA group, when compared with the model group, the grid error rate and the dragging rate of affected limb were decreased (P<0.01)；the utilization rate of affected limb and the percentage of blood perfusion were increased (P<0.05)；the content of serum IL-1ß was decreased (P<0.01), while the contents of TGF-ß and IL-10 were increased (P<0.01)；and the microglia in the primary motor cortex on the affected side got more round and were distributed more densely, the fluorescence intensity of IBA1 and CD206 was increased (P<0.01). CONCLUSIONS: Electroacupuncture preconditioning at "GV20" and "GV14" can up-regulate the expression of microglial cells, especially the M2 subtype cell marker, and increase the contents of the anti-inflammatory factors and decrease that of the pro-inflammatory factors in the serum, thereby alleviate the inflammatory reaction.

Ultra-early electroacupuncture rehabilitation for intravenous thrombolysis-induced cerebral infarction.

OBJECTIVE: The purpose of this research was to investigate whether it is possible to perform ultra-early interventional electroacupuncture on individuals who had experienced intravenous thrombolysis prior to receiving therapy for acute cerebral infarction. PATIENTS AND METHODS: Patients who have undergone intravenous thrombolysis between July 2019 and March 2021 were eligible for participation in this study. The participants were divided into two groups; one group received electroacupuncture therapy 24 hours after their condition became stable, while the other group received treatment 48 hours after their condition became stable. Both groups received the same therapy for their respective forms of rehabilitation. The Fugl-Meyer Motion Assessment Scale (FMA) was used to assess the patients' motor function before and after therapy, as well as two weeks and one month after treatment. The scores of the FMA were recorded before and after treatment. RESULTS: After therapy, the FMI scores were higher in both groups (p<0.05), and the researchers found that the ultra-early electroacupuncture intervention was related to higher FMI ratings 2 weeks and 1 month after treatment (p<0.05). In neither of the two study groups was there any sign of a major adverse response or consequence (p>0.05). CONCLUSIONS: This research offers evidence that ultra-early interventional electroacupuncture rehabilitation therapy may be an effective and safe method of treatment for individuals who have had a cerebral infarction after receiving intravenous thrombolysis. The results lend credence to the notion that this kind of therapy should be taken into consideration as an adjunctive model for rehabilitation in patients of this type.

Electroacupuncture promotes synaptic plasticity in rats with chronic inflammatory pain-related depression by upregulating BDNF/TrkB/CREB signaling pathway.

BACKGROUND: Chronic inflammatory pain (CIP) frequently coincides with depression among patients. The onset and development of pain and depression are associated with altered neural synaptic plasticity. Electroacupuncture (EA) can effectively relieve CIP and depression. However, the underlying mechanisms have not been fully illustrated. OBJECTIVE: To explore whether EA can relieve CIP and depression by regulating hippocampal synaptic plasticity, and the present study offers foundational evidence for the efficacy of EA in treating CIP-related depression (CIPD). METHODS: Rats were divided into four groups: 0.9% normal saline group, complete Freund's adjuvant (CFA) group, CFA + duloxetine group, and CFA + EA group. Pain hypersensitivity was detected by mechanical withdrawal threshold and thermal paw withdrawal latency, and the depression level was gauged using the open field test, the sucrose preference test, and the forced swimming test. The morphology of the hippocampal neurons was observed using Nissl staining. The protein expression levels of synuclein (Syn), postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factors (BDNFs), tyrosine-protein kinase B (TrKB), p-TrkB, cAMP response element binding protein (CREB), and p-CREB were measured by western blotting and immunofluorescence staining. BDNF and TrkB mRNA expression were detected using quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). The content of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) was detected using enzyme-linked immunosorbent assay, and the glutamic acid (Glu) content was determined using the ultraviolet colorimetry method. The hippocampal neuron ultrastructure was observed using transmission electron microscopy. RESULTS: EA could alleviate CIP and related depressive behaviors as well as protect the hippocampal neuronal structure from damage and regulate 5-HT/GABA/Glu levels in the hippocampus. Additionally, EA could significantly increase the expression of synapse-associated proteins such as PSD-95 and Syn by activating the BDNF/TrKB/CREB signaling pathway. CONCLUSION: EA improves pain and depressive behaviors in CIPD rats, and the mechanism may be related to synaptic plasticity mediated by the BDNF/TrKB/CREB signaling pathway.