反应性星形胶质细胞促进中风后的血管修复和重塑。

Reactive astrocytes facilitate vascular repair and remodeling after stroke.

机构信息

Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.

Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Cell Rep. 2021 Apr 27;35(4):109048. doi: 10.1016/j.celrep.2021.109048.

Abstract

Brain injury causes astrocytes to assume a reactive state that is essential for early tissue protection, but how reactive astrocytes affect later reparative processes is incompletely understood. In this study, we show that reactive astrocytes are crucial for vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data reveals substantial activation of transcriptional programs related to vascular remodeling after stroke. In vivo two-photon imaging provides evidence of astrocytes contacting newly formed vessels in cortex surrounding photothrombotic infarcts. Chemogenetic ablation of a subset of reactive astrocytes after stroke dramatically impairs vascular and extracellular matrix remodeling. This disruption of vascular repair is accompanied by prolonged blood flow deficits, exacerbated vascular permeability, ongoing cell death, and worsened motor recovery. In contrast, vascular structure in the non-ischemic brain is unaffected by focal astrocyte ablation. These findings position reactive astrocytes as critical cellular mediators of functionally important vascular remodeling during neural repair.

摘要

脑损伤会导致星形胶质细胞呈现出一种反应状态,这种状态对于早期的组织保护至关重要,但反应性星形胶质细胞如何影响后期的修复过程还不完全清楚。在这项研究中,我们表明,反应性星形胶质细胞对于小鼠缺血性中风后血管的修复和重塑是至关重要的。对星形胶质细胞基因表达数据的分析揭示了中风后与血管重塑相关的转录程序的大量激活。体内双光子成像提供了证据,表明星形胶质细胞在光血栓梗死周围皮质中与新形成的血管接触。中风后化学遗传消融一部分反应性星形胶质细胞会显著损害血管和细胞外基质的重塑。这种血管修复的中断伴随着持续的血流不足、血管通透性增加、持续的细胞死亡和运动功能恢复的恶化。相比之下,非缺血性大脑中的血管结构不受局灶性星形胶质细胞消融的影响。这些发现将反应性星形胶质细胞定位为神经修复过程中功能性重要血管重塑的关键细胞介质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/481c/8142687/8435942d9c67/nihms-1698680-f0002.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索