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Open Access 01-12-2019 | Stroke | Research

The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke

Authors: Yilong Shan, Sha Tan, Yinyao Lin, Siyuan Liao, Bingjun Zhang, Xiaodong Chen, Jihui Wang, Zhezhi Deng, Qin Zeng, Lei Zhang, Yuge Wang, Xueqiang Hu, Wei Qiu, Lisheng Peng, Zhengqi Lu

Published in: Journal of Neuroinflammation | Issue 1/2019

Abstract

Background

Preserving the integrity of the blood-brain barrier (BBB) is beneficial to avoid further brain damage after acute ischemic stroke (AIS). Astrocytes, an important component of the BBB, promote BBB breakdown in subjects with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the effect of Ex-4 on astrocytes in subjects with AIS remains unclear.

Methods

In the present study, we investigated the effect of Ex-4 on astrocytes cultured under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and determined whether the effect influences bEnd.3 cells. We used various methods, including permeability assays, western blotting, immunofluorescence staining, and gelatin zymography, in vitro and in vivo.

Results

Ex-4 reduced OGD-induced astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit scores, reduced the infarct area, and ameliorated BBB breakdown as well as decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes following OGD.

Conclusion

Based on these findings, ischemia-induced inflammation and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.

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Title: The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke
Authors: Yilong Shan
Sha Tan
Yinyao Lin
Siyuan Liao
Bingjun Zhang
Xiaodong Chen
Jihui Wang
Zhezhi Deng
Qin Zeng
Lei Zhang
Yuge Wang
Xueqiang Hu
Wei Qiu
Lisheng Peng
Zhengqi Lu
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Stroke
Published in: Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-019-1638-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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