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      The role of astrocytes in oxidative stress of central nervous system: A mixed blessing

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          Abstract

          Central nervous system (CNS) maintains a high level of metabolism, which leads to the generation of large amounts of free radicals, and it is also one of the most vulnerable organs to oxidative stress. Emerging evidences have shown that, as the key homeostatic cells in CNS, astrocytes are deeply involved in multiple aspects of CNS function including oxidative stress regulation. Besides, the redox level in CNS can in turn affect astrocytes in morphology and function. The complex and multiple roles of astrocytes indicate that their correct performance is crucial for the normal functioning of the CNS, and its dysfunction may result in the occurrence and progression of various neurological disorders. To date, the influence of astrocytes in CNS oxidative stress is rarely reviewed. Therefore, in this review we sum up the roles of astrocytes in redox regulation and the corresponding mechanisms under both normal and different pathological conditions.

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          Most cited references111

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          Physiology of Astroglia.

          Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.
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            Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury.

            Astroglial scars surround damaged tissue after trauma, stroke, infection, or autoimmune inflammation in the CNS. They are essential for wound repair, but also interfere with axonal regrowth. A better understanding of the cellular mechanisms, regulation, and functions of astroglial scar formation is fundamental to developing safe interventions for many CNS disorders. We used wild-type and transgenic mice to quantify and dissect these parameters. Adjacent to crush spinal cord injury (SCI), reactive astrocytes exhibited heterogeneous phenotypes as regards proliferation, morphology, and chemistry, which all varied with distance from lesions. Mature scar borders at 14 d after SCI consisted primarily of newly proliferated astroglia with elongated cell processes that surrounded large and small clusters of inflammatory, fibrotic, and other cells. During scar formation from 5 to 14 d after SCI, cell processes deriving from different astroglia associated into overlapping bundles that quantifiably reoriented and organized into dense mesh-like arrangements. Selective deletion of STAT3 from astroglia quantifiably disrupted the organization of elongated astroglia into scar borders, and caused a failure of astroglia to surround inflammatory cells, resulting in increased spread of these cells and neuronal loss. In cocultures, wild-type astroglia spontaneously corralled inflammatory or fibromeningeal cells into segregated clusters, whereas STAT3-deficient astroglia failed to do so. These findings demonstrate heterogeneity of reactive astroglia and show that scar borders are formed by newly proliferated, elongated astroglia, which organize via STAT3-dependent mechanisms to corral inflammatory and fibrotic cells into discrete areas separated from adjacent tissue that contains viable neurons.
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              Inflammasomes in the CNS.

              Microglia and macrophages in the CNS contain multimolecular complexes termed inflammasomes. Inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases, including meningitis, stroke and Alzheimer's disease. Assembly of an inflammasome activates caspase 1 and, subsequently, the proteolysis and release of the cytokines interleukin-1β and interleukin-18, as well as pyroptotic cell death. Since the discovery of inflammasomes in 2002, there has been burgeoning recognition of their complexities and functions. Here, we review the current understanding of the functions of different inflammasomes in the CNS and their roles in neurological diseases.
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                Author and article information

                Contributors
                aipingtong@scu.edu.cn
                liangxue_zhou@126.com
                Journal
                Cell Prolif
                Cell Prolif
                10.1111/(ISSN)1365-2184
                CPR
                Cell Proliferation
                John Wiley and Sons Inc. (Hoboken )
                0960-7722
                1365-2184
                08 February 2020
                March 2020
                : 53
                : 3 ( doiID: 10.1111/cpr.v53.3 )
                : e12781
                Affiliations
                [ 1 ] Department of Neurosurgery West China Medical School West China Hospital Sichuan University Chengdu China
                [ 2 ] State Key Laboratory of Biotherapy West China Medical School Sichuan University Chengdu China
                Author notes
                [*] [* ] Correspondence

                Aiping Tong, PhD, State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, No. 37 Guo Xue Xiang Chengdu, Sichuan 610041, China.

                Email: aipingtong@ 123456scu.edu.cn

                Liangxue Zhou, PhD, Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang Chengdu, Sichuan 610041, China.

                Email: liangxue_zhou@ 123456126.com

                Author information
                https://orcid.org/0000-0003-2532-9294
                Article
                CPR12781
                10.1111/cpr.12781
                7106951
                32035016
                e7d64af8-8d2d-49ed-8ce7-842c29cceabd
                © 2020 The Authors. Cell Proliferation 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
                : 09 November 2019
                : 17 December 2019
                : 20 January 2020
                Page count
                Figures: 3, Tables: 0, Pages: 13, Words: 9635
                Funding
                Funded by: 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University
                Award ID: ZYJC18007
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 31471286
                Award ID: 81772693
                Funded by: National Major Scientific and Technological Special Project for Significant New Drugs Development
                Award ID: 2019ZX09301‐147
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                March 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.8 mode:remove_FC converted:31.03.2020

                Cell biology
                astrocyte,astrogliosis,central nervous system,oxidative stress,rns,ros
                Cell biology
                astrocyte, astrogliosis, central nervous system, oxidative stress, rns, ros

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