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.

中文翻译：

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Dectin-1 / Syk信号传导在小鼠缺血性中风后触发神经炎症。

背景技术据报道，与树突状细胞相关的C型凝集素-1（Dectin-1）受体与阿尔茨海默氏病和脑外伤中的神经炎症有关。本研究旨在使用局灶性皮质缺血性卒中模型调查Dectin-1及其下游靶标脾酪氨酸激酶（Syk）在缺血性卒中后早期脑损伤中的作用。方法对成年雄性C57BL / 6 J小鼠进行缺血性脑卒中的脑局灶性缺血模型。在缺血性卒中后第1、3、5和7天评估神经学评分，脱粘剂测试和断脚测试。Dectin-1，Syk，磷酸化（p）-Syk，肿瘤坏死因子-α（TNF-α），并通过蛋白质印迹分析了缺血性中风后缺血性脑组织中和体外受氧-葡萄糖剥夺/复氧（OGD / R）损伤的BV2小胶质细胞中诱导型一氧化氮合酶（iNOS）的表达。分别使用尼氏染色和免疫荧光染色评估脑梗死体积和Iba1阳性细胞。Dectin-1拮抗剂laminarin（LAM）和Syk磷酸化的选择性抑制剂（piceatannol; PIC）用于干预。结果Dectin-1，Syk和p-Syk表达在缺血性中风后第3、5和7天显着增强，并在第3天达到高峰。Dectin-1拮抗剂LAM或Syk抑制剂PIC减少了Iba1阳性细胞的数量以及TNF-α和iNOS的表达，减少了脑梗死的体积，缺血性中风后第3天神经功能得到改善。此外，体外数据显示，在BV2小胶质细胞中进行3小时的OGD以及0、3和6小时的再灌注后，Dectin-1，Syk和p-Syk的表达增加。OGD / R诱导后3小时，LAM和PIC也降低TNF-α和iNOS表达。结论Dectin-1 / Syk信号传导在缺血性中风后的炎症激活中起着至关重要的作用，因此有必要进一步研究卒中中的Dectin-1 / Syk信号传导。