He Tingting, Yang Guo-Yuan, Zhang Zhijun
Department of Neurology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
Neuroscience and Neuroengineering Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Life (Basel). 2022 Jun 17;12(6):910. doi: 10.3390/life12060910.
Stroke is a leading cause of death and long-term disability worldwide. Astrocytes structurally compose tripartite synapses, blood-brain barrier, and the neurovascular unit and perform multiple functions through cell-to-cell signaling of neurons, glial cells, and vasculature. The crosstalk of astrocytes and other cells is complicated and incompletely understood. Here we review the role of astrocytes in response to ischemic stroke, both beneficial and detrimental, from a cell-cell interaction perspective. Reactive astrocytes provide neuroprotection through antioxidation and antiexcitatory effects and metabolic support; they also contribute to neurorestoration involving neurogenesis, synaptogenesis, angiogenesis, and oligodendrogenesis by crosstalk with stem cells and cell lineage. In the meantime, reactive astrocytes also play a vital role in neuroinflammation and brain edema. Glial scar formation in the chronic phase hinders functional recovery. We further discuss astrocyte enriched microRNAs and exosomes in the regulation of ischemic stroke. In addition, the latest notion of reactive astrocyte subsets and astrocytic activity revealed by optogenetics is mentioned. This review discusses the current understanding of the intimate molecular conversation between astrocytes and other cells and outlines its potential implications after ischemic stroke. "Neurocentric" strategies may not be sufficient for neurological protection and recovery; future therapeutic strategies could target reactive astrocytes.
中风是全球范围内导致死亡和长期残疾的主要原因。星形胶质细胞在结构上构成三联突触、血脑屏障和神经血管单元，并通过神经元、胶质细胞和脉管系统之间的细胞间信号传导发挥多种功能。星形胶质细胞与其他细胞之间的相互作用复杂，尚未完全明确。在此，我们从细胞间相互作用的角度综述星形胶质细胞在缺血性中风中的作用，包括有益和有害的方面。反应性星形胶质细胞通过抗氧化和抗兴奋作用以及代谢支持提供神经保护；它们还通过与干细胞和细胞谱系的相互作用，在涉及神经发生、突触形成、血管生成和少突胶质细胞生成的神经修复中发挥作用。与此同时，反应性星形胶质细胞在神经炎症和脑水肿中也起着至关重要的作用。慢性期的胶质瘢痕形成会阻碍功能恢复。我们进一步讨论了星形胶质细胞富集的微小RNA和外泌体在缺血性中风调节中的作用。此外，还提到了光遗传学揭示的反应性星形胶质细胞亚群和星形胶质细胞活性的最新概念。本综述讨论了目前对星形胶质细胞与其他细胞之间密切分子对话的理解，并概述了其在缺血性中风后的潜在影响。“以神经元为中心”的策略可能不足以实现神经保护和恢复；未来的治疗策略可能以反应性星形胶质细胞为靶点。
