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Open Access 01-12-2020 | Stroke | Research

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Authors: Xin-Chun Ye, Qi Hao, Wei-Jing Ma, Qiu-Chen Zhao, Wei-Wei Wang, Han-Han Yin, Tao Zhang, Miao Wang, Kun Zan, Xin-Xin Yang, Zuo-Hui Zhang, Hong-Juan Shi, Jie Zu, Hafiz Khuram Raza, Xue-Ling Zhang, De-Qin Geng, Jin-Xia Hu, Gui-Yun Cui

Published in: Journal of Neuroinflammation | Issue 1/2020

Abstract

Background

Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer’s disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model.

Methods

Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl’s and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention.

Results

Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction.

Conclusion

Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

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Title: Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice
Authors: Xin-Chun Ye
Qi Hao
Wei-Jing Ma
Qiu-Chen Zhao
Wei-Wei Wang
Han-Han Yin
Tao Zhang
Miao Wang
Kun Zan
Xin-Xin Yang
Zuo-Hui Zhang
Hong-Juan Shi
Jie Zu
Hafiz Khuram Raza
Xue-Ling Zhang
De-Qin Geng
Jin-Xia Hu
Gui-Yun Cui
Publication date: 01-12-2020
Publisher: BioMed Central
Keyword: Stroke
Published in: Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-019-1693-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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