Journal of Neuroinflammation (Jan 2020)

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

  • 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

DOI
https://doi.org/10.1186/s12974-019-1693-z
Journal volume & issue
Vol. 17, no. 1
pp. 1 – 16

Abstract

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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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