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      No‐reflow after stroke reperfusion therapy: An emerging phenomenon to be explored

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          Abstract

          In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the “no‐reflow phenomenon” or “microvascular obstruction,” was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no‐reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no‐reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.

          Abstract

          The illustration of the consequences, pathogenesis, diagnostic methods, and promising management of the cerebral no‐reflow phenomenon.

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          Most cited references114

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          Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

          Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.
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            Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

            In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included.
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              Capillary pericytes regulate cerebral blood flow in health and disease

              Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.
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                Author and article information

                Contributors
                zhaowb@xwh.ccmu.edu.cn
                jixm@ccmu.edu.cn
                Journal
                CNS Neurosci Ther
                CNS Neurosci Ther
                10.1111/(ISSN)1755-5949
                CNS
                CNS Neuroscience & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                1755-5930
                1755-5949
                15 February 2024
                February 2024
                : 30
                : 2 ( doiID: 10.1002/cns.v30.2 )
                : e14631
                Affiliations
                [ 1 ] Department of Neurology, Xuanwu Hospital Capital Medical University Beijing China
                [ 2 ] Department of Emergency, Xuanwu Hospital Capital Medical University Beijing China
                [ 3 ] Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital Capital Medical University Beijing China
                [ 4 ] Department of Neurosurgery Wayne State University School of Medicine Detroit Michigan USA
                [ 5 ] Department of Neurosurgery, Xuanwu Hospital Capital Medical University Beijing China
                Author notes
                [*] [* ] Correspondence

                Wenbo Zhao, Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053, China.

                Email: zhaowb@ 123456xwh.ccmu.edu.cn

                Xunming Ji, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing 100053, China.

                Email: jixm@ 123456ccmu.edu.cn

                Author information
                https://orcid.org/0000-0002-3030-5302
                https://orcid.org/0000-0001-5358-1660
                https://orcid.org/0000-0003-0293-2744
                Article
                CNS14631 CNSNT-2023-896.R1
                10.1111/cns.14631
                10867879
                38358074
                06bf189e-cd01-422f-b4e6-3839638a0d51
                © 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 January 2024
                : 27 June 2023
                : 21 January 2024
                Page count
                Figures: 3, Tables: 1, Pages: 12, Words: 8273
                Funding
                Funded by: Beijing Natural Science Foundation , doi 10.13039/501100004826;
                Award ID: JQ22020
                Funded by: Beijing Nova Program , doi 10.13039/501100005090;
                Award ID: Z201100006820143
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81801313
                Award ID: 82001257
                Award ID: 81971114
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                February 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.8 mode:remove_FC converted:15.02.2024

                Neurosciences
                acute ischemic stroke,endovascular thrombectomy,microvascular disturbance,no‐reflow phenomenon,reperfusion therapy

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