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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3/STAT3 pathway

Authors: Ran Li, Wenchao Liu, Jian Yin, Yunchang Chen, Shenquan Guo, Haiyan Fan, Xifeng Li, Xin Zhang, Xuying He, Chuanzhi Duan

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

An acute and drastic inflammatory response characterized by the production of inflammatory mediators is followed by stroke, including SAH. Overactivation of microglia parallels an excessive inflammatory response and worsened brain damage. Previous studies indicate that TSG-6 has potent immunomodulatory and anti-inflammatory properties. This study aimed to evaluate the effects of TSG-6 in modulating immune reaction and microglial phenotype shift after experimental SAH.

Methods

The SAH model was established by endovascular puncture method for Sprague–Dawley rats (weighing 280–320 g). Recombinant human protein and specific siRNAs for TSG-6 were exploited in vivo. Brain injury was assessed by neurologic scores, brain water content, and Fluoro-Jade C (FJC) staining. Microglia phenotypic status was evaluated and determined by Western immunoblotting, quantitative real-time polymerase chain reaction (qPCR) analyses, flow cytometry, and immunofluorescence labeling.

Results

SAH induced significant inflammation, and M1-dominated microglia polarization increased expression of TSG-6 and neurological dysfunction in rats. rh-TSG-6 significantly ameliorated brain injury, decreased proinflammatory mediators, and skewed microglia towards a more anti-inflammatory property 24-h after SAH. While knockdown of TSG-6 further induced detrimental effects of microglia accompanied with more neurological deficits, the anti-inflammation effects of rh-TSG-6 were associated with microglia phenotypic shift by regulating the level of SOCS3/STAT3 axis.

Conclusions

TSG-6 exerted neuroprotection against SAH-induced EBI in rats, mediated in part by skewing the balance of microglial response towards a protective phenotype, thereby preventing excessive tissue damage and improving functional outcomes. Our findings revealed the role of TSG-6 in modulating microglial response partially involved in the SOCS3/STAT3 pathway and TSG-6 may be a promising therapeutic target for the treatment of brain injury following SAH.
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Metadata
Title
TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3/STAT3 pathway
Authors
Ran Li
Wenchao Liu
Jian Yin
Yunchang Chen
Shenquan Guo
Haiyan Fan
Xifeng Li
Xin Zhang
Xuying He
Chuanzhi Duan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1279-1

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