Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
J Neurotrauma. 2020 Mar 1;37(5):681-691. doi: 10.1089/neu.2019.6938.
Reactive astrocytes have traditionally been viewed as a significant contributor to secondary neuronal damage and repair inhibition after central nervous system (CNS) injury attributed, in large part, to their roles in glial scarring. However, more recent transcriptional evidence has uncovered the vast diversity in reactive astrocyte identity and functions that comprises both neuroprotective and -toxic characteristics. Additionally, the capacity of reactive astrocytes to shift between these activation states demonstrates a high level of environment-dependent plasticity that drives the interplay between neuroprotection and -toxicity after CNS injury. These recent findings have spawned a new field of research that seeks to identify and categorize the function of these discrete subpopulations in the context of neurotrauma, as well as identify their regulators. Therefore, this review will discuss the major and most recent advances in this field of research, with a primary emphasis on neuroprotection. This review will also discuss the major pitfalls present in the field, with a particular focus on model species and their impact on the development of novel therapies.
传统上，反应性星形胶质细胞被认为是中枢神经系统 (CNS) 损伤后继发性神经元损伤和修复抑制的重要贡献者，这在很大程度上归因于它们在神经胶质瘢痕形成中的作用。然而，最近的转录证据揭示了反应性星形胶质细胞身份和功能的巨大多样性，包括神经保护和神经毒性特征。此外，反应性星形胶质细胞在这些激活状态之间转换的能力表明了高度依赖环境的可塑性，这种可塑性驱动了 CNS 损伤后神经保护和神经毒性之间的相互作用。这些新发现催生了一个新的研究领域，旨在在神经创伤的背景下识别和分类这些离散亚群的功能，并确定它们的调节剂。因此，本综述将讨论该领域的主要和最新进展，主要重点是神经保护。本综述还将讨论该领域存在的主要缺陷，特别关注模型物种及其对新型治疗方法发展的影响。
