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BACKGROUND: Electroacupuncture (EA) is a promising alternative therapy for migraine, with mitochondrial dysfunction hypothesized as a pivotal mechanism in migraine pathophysiology. This research endeavors to investigate the therapeutic potential of EA in addressing migraines and shed light on the associated mechanisms linked to mitochondrial anomalies. MATERIALS AND METHODS: Migraine in rats was induced by 10 mg/kg nitroglycerin, followed by 2/15 Hz EA treatment at GB20 and LR3. Nociceptive behavior was recorded via a camera and analyzed using EthoVision XT 12.0 software. The hind-paw withdrawal threshold was assessed using the von Frey test. We assessed the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), and endothelin (ET) - key parameters in migraine pathophysiology using immunohistochemistry and enzyme-linked immunosorbent assay. Mitochondrial morphology in brain tissues was observed through transmission electron microscopy. Reactive oxygen species (ROS) level in mitochondria was measured by flow cytometry. The levels of PINK1 and Parkin were assessed using Western blot analysis. RESULTS: EA at GB20 and LR3 decreased nociceptive behaviors (resting and grooming) and increased exploratory and locomotor behaviors in migraine rats. The hind-paw withdrawal threshold in migraine rats was significantly elevated following EA treatment. Post-EA treatment, levels of CGRP and NO decreased, while ET level increased, suggesting an alteration in pain and vascular physiology. Notably, EA treatment mitigated the mitochondrial damage and reduced ROS level in the brain tissues of migraine rats. EA treatment upregulated the expression of PINK1 and Parkin in migraine rats. CONCLUSION: EA at GB20 and LR3 may treat migraine by alleviating PINK1/Parkin-mediated mitochondrial dysfunction.
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Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, its specific anti-IS mechanisms remain to be fully elucidated. By constructing a rat IS (middle cerebral artery occlusion, or MCAO) model and performing EA treatment, neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in the rat brain penumbra were assessed by western blotting. Following EA treatment, neurological deficit scores, brain water content, cerebral infarction area, and GFAP, Iba-1, and Nestin expression were reduced. Additionally, EA treatment decreased MDA and increased SOD, GSH, and CAT. Moreover, the rats showed elevated GPX4 and SLC7A11 and lowered TfR1, L-ferritin, and hepcidin. In contrast, a7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated. EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.
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Electroacupuntura , Ferroptosis , Accidente Cerebrovascular Isquémico , Estrés Oxidativo , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Ratas , Serina-Treonina Quinasas TOR/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/terapia , Modelos Animales de Enfermedad , Masculino , Humanos , Ratas Sprague-DawleyRESUMEN
Post-stroke cognitive impairment is a significant challenge with limited treatment options. Electroacupuncture (EA) has shown promise in improving cognitive function after stroke. Our study explores the underlying mechanism of EA in alleviating cognitive impairment through the inhibition of autophagy. We utilized a rat model of stroke induced by middle cerebral artery occlusion (MCAO) to evaluate the efficacy of EA. Treatment with EA was observed to markedly improve cognitive function and reduce inflammation in MCAO rats, as evidenced by decreased neurological deficit scores, shorter latencies in the water maze test, and diminished infarct volumes. EA also attenuated tissue damage in the hippocampus and lowered the levels of pro-inflammatory cytokines and oxidative stress markers. Although autophagy was upregulated in MCAO rats, EA treatment suppressed this process, indicated by a reduction in autophagosome formation and alteration of autophagy-related protein expression. The protective effects of EA were reversed by the autophagy activator rapamycin. EA treatment elevated the levels of microRNA (miR)-135a-5p expression, and suppression of this elevation attenuated the remedial efficacy of EA in addressing cognitive impairment and inflammation. MiR-135a-5p targeted mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling to repress autophagy. EA treatment inhibits autophagy and alleviates cognitive impairment in post-stroke rats. It exerts its beneficial effects by upregulating miR-135a-5p and targeting the mTOR/NLRP3 axis.
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Autofagia , Disfunción Cognitiva , Electroacupuntura , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Serina-Treonina Quinasas TOR , Animales , Masculino , Ratas , Autofagia/fisiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Electroacupuntura/métodos , Hipocampo/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/metabolismo , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
OBJECTIVE: To compare the effect of micro-needle knife therapy and betahistine mesilate tablets in the treatment of cervical vertigo (CV) and the influence on the mean blood flow velocity (Vm) of vertebral artery. METHODS: A total of 200 patients with CV were randomly divided into a micro-needle knife group (100 cases, 5 cases dropped off) and a medication group (100 cases, 3 cases dropped off). In the micro-needle knife group, micro-needle knife was performed on the suboccipital triangle of the atlantoaxial segment of the posterior neck, once every other day, for a total of 7-time treatment. The medication group received oral betahistine mesilate tablets, 6 mg each time, three times a day, for 14 consecutive days. The dizziness handicap inventory (DHI) scores of the two groups were observed before treatment, after treatment and during follow-up 3 months after treatment; the Vm of vertebral artery was compared between the two groups before and after treatment, and the clinical effect was evaluated during follow-up. RESULTS: After treatment and during follow-up, the DHI scores of the two groups were lower than those before treatment (P<0.001), and those in the micro-needle knife group were lower than the medication group (P<0.001). After treatment, the Vm of bilateral vertebral arteries in both groups was higher than that before treatment (P<0.05), and that in the micro-needle knife group was higher than the medication group (P<0.05). The total effective rate of the micro-needle knife group was 96.8% (92/95), which was higher than 67.0% (65/97) of the medication group (P<0.001). CONCLUSION: Micro-needle knife therapy can improve vertigo symptoms and balance dysfunction, increase the mean blood flow velocity of vertebral artery in CV patients, and its clinical efficacy is better than oral betahistine mesilate tablets.
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Betahistina , Arteria Vertebral , Hemodinámica , Humanos , Mesilatos , Resultado del Tratamiento , Vértigo/etiología , Vértigo/terapiaRESUMEN
OBJECTIVE: To observe the clinical efficacy of micro needle knife therapy on cervical vertigo. METHODS: A total of 300 patients with cervical vertigo treated from January 1, 2017 to December 31, 2019 were randomly divided into micro needle knife group (96 cases, 4 cases falling off), traditional acupuncture group (96 cases, 4 cases falling off) and oral drug group(95 cases, 5 cases falling off). The micro needle knife group was treated with micro needle knife in the local upper cervical segment once every other day for 7 times; the traditional acupuncture group was treated with traditional acupuncture once a day for 2 weeks;the oral drug group was given Merislon (betahistine mesilate tablets) orally, 6 mg each time, 3 times a day for 2 weeks. The patients were followed up before treatment, at the end of treatment and 3 months after treatment. The dizziness handicap inventory(DHI) was observed and the curative effect was evaluated according to the DHI score. RESULTS: At the end of the course of treatment and 3 months after the treatment, DHI scores of the three groups were significantly lower than those before treatment(P<0.01), and the DHI scores of micro needle knife group were lower than those of traditional acupuncture group and oral drug group at the same time point after treatment (P<0.01). There was no statistically significant difference in DHI scores between traditional acupuncture group and oral drug group at the same time after treatment(P< 0.05). The curative effect was evaluated according to DHI score:in micro needle knife group, 50 cases were cured, 28 cases were markedly effective, 14 cases were improved, the total effective rate was 95.83%; in traditional acupuncture group, 28 cases were cured, 26 cases were markedly effective, and 24 cases were improved, with the total effective rate of 81.25%;in oral drug group, 18 cases were cured, 20 cases were markedly effective, and 28 cases were improved, with the total effective rate of 69.47%. The total effective rate of micro needle knife group was significantly higher than that of other two groups (χ2=45.956, P=0.000). Among the cured patients in the three groups, the time required in the micro needle knife group was significantly less than that in the traditional acupuncture group and oral drug group(F=18.796, P=0.000). CONCLUSION: Micro needle knife loosening atlantoaxial soft tissue has obvious curative effect on cervical vertigo which clinical cure rate, effective rate and treatment time required for cured patients are better than traditional acupuncture and oral drug.
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Terapia por Acupuntura , Vértigo , Estudios de Casos y Controles , Humanos , Agujas , Resultado del Tratamiento , Vértigo/terapiaRESUMEN
Mitochondrial dysfunction contributes to excessive reactive oxygen species (ROS) generation, which is a dramatic cause to promote endothelial dysfunction in diabetes. It was previously demonstrated that crocin protected the endothelium based on its diverse medicinal properties, but its effect on the mitochondrion and the potential mechanism are not fully understood. In this study, mitochondrial function was analyzed during the process of excessive ROS generation in high glucose (HG)-cultured human umbilical vein endothelial cells (HUVECs). The role played by KCa3.1 was further investigated by the inhibition and/or gene silence of KCa3.1 in this process. In addition, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase 2 (NOX2), superoxide dismutase 1 (SOD1), and glutathione peroxidase 1 (GPx1) were also detected in this study. Our data showed that crocin improved mitochondrial dysfunction and maintained normal mitochondrial morphology by enhancing the mitochondrial membrane potential (MMP), mitochondrial mass, and mitochondrial fusion. Furthermore, KCa3.1 was confirmed to be located in the mitochondrion, and the blockade and/or silencing of KCa3.1 improved mitochondrial dysfunction and reduced excessive ROS generation but did not affect NOX2 and/or the SOD1 system. Intriguingly, it was confirmed that KCa3.1 expression was elevated by ROS overproduction in the endothelium under HG and/or diabetes conditions, while crocin significantly suppressed this elevation by promoting GPx1 and subsequently eliminating ROS generation. In addition, crocin enhanced CD31, thrombomodulin (TM), and p-/t-endothelial nitric oxide synthase (eNOS) expressions as well as NO generation and decreased vascular tone. Hence, crocin improved mitochondrial dysfunction through inhibiting ROS-induced KCa3.1 overexpression in the endothelium, which in turn reduced more ROS generation and final endothelial dysfunction in diabetes.