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Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair
Journal of Neuroscience Research ( IF 4.2 ) Pub Date : 2021-07-14 , DOI: 10.1002/jnr.24922
Christopher G Hart 1 , Soheila Karimi-Abdolrezaee 1
Affiliation  

Astrocytes play essential roles in development, homeostasis, injury, and repair of the central nervous system (CNS). Their development is tightly regulated by distinct spatial and temporal cues during embryogenesis and into adulthood throughout the CNS. Astrocytes have several important responsibilities such as regulating blood flow and permeability of the blood-CNS barrier, glucose metabolism and storage, synapse formation and function, and axon myelination. In CNS pathologies, astrocytes also play critical parts in both injury and repair mechanisms. Upon injury, they undergo a robust phenotypic shift known as “reactive astrogliosis,” which results in both constructive and deleterious outcomes. Astrocyte activation and migration at the site of injury provides an early defense mechanism to minimize the extent of injury by enveloping the lesion area. However, astrogliosis also contributes to the inhibitory microenvironment of CNS injury and potentiate secondary injury mechanisms, such as inflammation, oxidative stress, and glutamate excitotoxicity, which facilitate neurodegeneration in CNS pathologies. Intriguingly, reactive astrocytes are increasingly a focus in current therapeutic strategies as their activation can be modulated toward a neuroprotective and reparative phenotype. This review will discuss recent advancements in knowledge regarding the development and role of astrocytes in the healthy and pathological CNS. We will also review how astrocytes have been genetically modified to optimize their reparative potential after injury, and how they may be transdifferentiated into neurons and oligodendrocytes to promote repair after CNS injury and neurodegeneration.

中文翻译:

关于星形胶质细胞在 CNS 稳态、病理学和修复中的机制的最新见解

星形胶质细胞在中枢神经系统 (CNS) 的发育、体内平衡、损伤和修复中发挥重要作用。它们的发育受到胚胎发育期间和整个 CNS 成年期不同的空间和时间线索的严格调控。星形胶质细胞有几个重要的职责,例如调节血液-CNS 屏障的血流和通透性、葡萄糖代谢和储存、突触的形成和功能以及轴突髓鞘形成。在中枢神经系统病理学中,星形胶质细胞也在损伤和修复机制中发挥关键作用。受伤后,它们会经历一种称为“反应性星形胶质细胞增生”的强大表型转变,这会导致建设性和有害的结果。损伤部位的星形胶质细胞活化和迁移提供了一种早期防御机制,通过包裹病变区域来最大限度地减少损伤程度。然而,星形胶质细胞增生也有助于中枢神经系统损伤的抑制性微环境,并增强继发性损伤机制,如炎症、氧化应激和谷氨酸兴奋性毒性,从而促进中枢神经系统病理的神经退行性变。有趣的是,反应性星形胶质细胞越来越成为当前治疗策略的焦点,因为它们的激活可以被调节为神经保护和修复表型。本综述将讨论有关星形胶质细胞在健康和病理性中枢神经系统中的发育和作用方面的最新进展。我们还将回顾星形胶质细胞如何进行基因改造以优化其受伤后的修复潜力,
更新日期:2021-07-14
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