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      Electroacupuncture Preconditioning Reduces Oxidative Stress in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats by Regulating Iron Metabolism Pathways

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          Abstract

          Background

          Oxidative stress is an important mechanism of cerebral ischemia-reperfusion injury. Ferroptosis caused by iron overload after cerebral ischemia-reperfusion is considered a common cause of oxidative stress. Many recent studies have shown that electroacupuncture (EA) can regulate the expression of inflammatory factors, and the use of electroacupuncture preconditioning can produce a protective effect, which can reduce injury after cerebral ischemia and reperfusion. We aimed to assess whether EA could be used to reduce oxidative stress.

          Methods

          The oxidative stress level of rats during the acute phase of cerebral ischemia and reperfusion was assessed with and without preconditioning with EA. Molecular biology methods were used to detect iron metabolism and oxidative stress-related proteins.

          Results

          Rats that had EA preconditioning had lower infarct volumes than rats in the control group. Furthermore, western blot analysis showed that the expression of iron metabolism-related protein FPN-1 was higher in the intervention group than in the model group after reperfusion. In this regard, further investigation also demonstrated higher expression of glutathione and glutathione peroxidase-4, and lower reactive oxygen species values in the brain tissue of the EA group were compared with those of the control group rats.

          Conclusions

          Electroacupuncture preconditioning can reduce oxidative stress after cerebral ischemia-reperfusion by regulating iron overload.

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          Most cited references45

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          Ischemia and reperfusion--from mechanism to translation.

          Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion-associated tissue inflammation and organ dysfunction.
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            Lipid peroxidation and ferroptosis: The role of GSH and GPx4.

            Ferroptosis (FPT) is a form of cell death due to missed control of membrane lipid peroxidation (LPO). According to the axiomatic definition of non-accidental cell death, LPO takes place in a scenario of altered homeostasis. FPT, differently from apoptosis, occurs in the absence of any known specific genetically encoded death pathway or specific agonist, and thus must be rated as a regulated, although not "programmed", death pathway. It follows that LPO is under a homeostatic metabolic control and is only permitted when indispensable constraints are satisfied and the antiperoxidant machinery collapses. The activity of the selenoperoxidase Glutathione Peroxidase 4 (GPx4) is the cornerstone of the antiperoxidant defence. Converging evidence on both mechanism of LPO and GPx4 enzymology indicates that LPO is initiated by alkoxyl radicals produced by ferrous iron from the hydroperoxide derivatives of lipids (LOOH), traces of which are the unavoidable drawback of aerobic metabolism. FPT takes place when a threshold has been exceeded. This occurs when the major conditions are satisfied: i) oxygen metabolism leading to the continuous formation of traces of LOOH from phospholipid-containing polyunsaturated fatty acids; ii) missed enzymatic reduction of LOOH; iii) availability of ferrous iron from the labile iron pool. Although the effectors impacting on homeostasis and leading to FPT in physiological conditions are not known, from the available knowledge on LPO and GPx4 enzymology we propose that it is aerobic life itself that, while supporting bioenergetics, is also a critical requisite of FPT. Yet, when the homeostatic control of the steady state between LOOH formation and reduction is lost, LPO is activated and FPT is executed.
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              Stroke

              Stroke is a major cause of death and disability globally. Diagnosis depends on clinical features and brain imaging to differentiate between ischaemic stroke and intracerebral haemorrhage. Non-contrast CT can exclude haemorrhage, but the addition of CT perfusion imaging and angiography allows a positive diagnosis of ischaemic stroke versus mimics and can identify a large vessel occlusion target for endovascular thrombectomy. Management of ischaemic stroke has greatly advanced, with rapid reperfusion by use of intravenous thrombolysis and endovascular thrombectomy shown to reduce disability. These therapies can now be applied in selected patients who present late to medical care if there is imaging evidence of salvageable brain tissue. Both haemostatic agents and surgical interventions are investigational for intracerebral haemorrhage. Prevention of recurrent stroke requires an understanding of the mechanism of stroke to target interventions, such as carotid endarterectomy, anticoagulation for atrial fibrillation, and patent foramen ovale closure. However, interventions such as lowering blood pressure, smoking cessation, and lifestyle optimisation are common to all stroke subtypes.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2021
                8 November 2021
                8 November 2021
                : 2021
                : 3056963
                Affiliations
                1Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
                2Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
                3Fourth Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
                Author notes

                Academic Editor: Feng Zhang

                Author information
                https://orcid.org/0000-0002-9184-5097
                https://orcid.org/0000-0003-0239-6072
                https://orcid.org/0000-0001-7618-6022
                https://orcid.org/0000-0002-6884-6438
                https://orcid.org/0000-0002-8995-1931
                https://orcid.org/0000-0003-4638-7004
                Article
                10.1155/2021/3056963
                8592755
                34790244
                783c9e96-3fe0-48bb-b58e-15719ecd6db8
                Copyright © 2021 Runyu Liang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 September 2021
                : 8 October 2021
                : 25 October 2021
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82174477
                Funded by: Young Talents Promotion Project of the China Association of Traditional Chinese Medicine
                Award ID: CACM-2019-QNRC2-B04
                Funded by: Heilongjiang University of Traditional Chinese Medicine
                Award ID: 2019JC03
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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