The Specific Role of Reactive Astrocytes in Stroke.

Leiyang Li,Haixiao Liu,Shenghao Zhang,Liying Han,Jinpeng Zhou,Qing Hu,Yan Qu,Wenxing Cui,Jin Wang,Dayun Feng,Wei Guo,Xun Wu,Hao Bai,Yingwu Shi

doi:10.3389/fncel.2022.850866

Leiyang Li, Haixiao Liu + Show 12 more

Open Access

https://doi.org/10.3389/fncel.2022.850866

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Abstract

Astrocytes are essential in maintaining normal brain functions such as blood brain barrier (BBB) homeostasis and synapse formation as the most abundant cell type in the central nervous system (CNS). After the stroke, astrocytes are known as reactive astrocytes (RAs) because they are stimulated by various damage-associated molecular patterns (DAMPs) and cytokines, resulting in significant changes in their reactivity, gene expression, and functional characteristics. RAs perform multiple functions after stroke. The inflammatory response of RAs may aggravate neuro-inflammation and release toxic factors to exert neurological damage. However, RAs also reduce excitotoxicity and release neurotrophies to promote neuroprotection. Furthermore, RAs contribute to angiogenesis and axonal remodeling to promote neurological recovery. Therefore, RAs’ biphasic roles and mechanisms make them an effective target for functional recovery after the stroke. In this review, we summarized the dynamic functional changes and internal molecular mechanisms of RAs, as well as their therapeutic potential and strategies, in order to comprehensively understand the role of RAs in the outcome of stroke disease and provide a new direction for the clinical treatment of stroke.

Highlights

Stroke is an acute cerebrovascular disease in which the blood cannot supply the brain generally due to the sudden rupture or blockage of the cerebrovascular
glial fibrillary acidic protein (GFAP) mRNA and protein expression were significantly up-regulated in astrocytes under various injury factors, so GFAP was considered a universal marker of reactive astrocytes (RAs) in initial studies
Our study found that proteinase-activated receptor 4 (PAR4) expressed on the cell membrane of astrocytes detects thrombin released by tissues and activates Tab2/NF-κB signaling pathway to initiate inflammatory injury mechanism (Luo et al, 2021)

Summary

Introduction

Stroke is an acute cerebrovascular disease in which the blood cannot supply the brain generally due to the sudden rupture or blockage of the cerebrovascular. GFAP mRNA and protein expression were significantly up-regulated in astrocytes under various injury factors, so GFAP was considered a universal marker of RAs in initial studies.

Results

Conclusion