As an endogenous activator of toll-like receptor-4 (Tlr4), the extracellular matrix glycoprotein tenascin-C (TnC) regulates chemotaxis, phagocytosis and proinflammatory cytokine production in microglia. The role of TnC for ischemic brain injury, post-ischemic immune responses and stroke recovery has still not been evaluated. By comparing wild type and TnC-/- mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO), we examined the effects of TnC deficiency for ischemic injury, neurological deficits, microglia/macrophage activation and brain leukocyte infiltration using behavioural tests, histochemical studies, Western blot, polymerase chain reaction and flow cytometry. Histochemical studies revealed that TnC was de novo expressed in the ischemic striatum, which contained the infarct core, and overlapped with the area of strongest accumulation of Iba1+ microglia/macrophages. TnC deficiency increased overall Iba1 immunoreactivity in the perilesional cortex, suggesting that TnC might restrict the distribution of microglial cells to the infarct core. By analysing microglial morphology in 3D we found that the post-ischemic loss of microglial cell territory, branching and volume at 3 and 7 days post-ischemia was amplified in the brains of TnC deficient compared with wild type mice. Microglial cell number was not different between genotypes. Hence, TnC deficiency reduced tissue surveillance by microglial cells. Concomitantly, the number of infiltrating leukocytes and, more specifically T cells, was increased in the ischemic brain parenchyma of TnC deficient compared with wild type mice. Ischemic injury and neurological deficits were not affected by TnC deficiency. We propose that the reduced microglia surveillance in TnC deficient mice might favour leukocyte accumulation in the ischemic brain.

中文翻译：

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生腱蛋白-C 保留小胶质细胞监测并限制白细胞，更具体地说，限制缺血性脑的 T 细胞浸润

作为 toll 样受体 4 (Tlr4) 的内源性激活剂，细胞外基质糖蛋白生腱蛋白-C (TnC) 在小胶质细胞中调节趋化性、吞噬作用和促炎细胞因子的产生。TnC 在缺血性脑损伤、缺血后免疫反应和中风恢复中的作用仍未得到评估。通过比较暴露于短暂腔内大脑中动脉闭塞 (MCAO) 的野生型和 TnC-/- 小鼠，我们使用行为测试、组织化学研究检查了 TnC 缺乏对缺血性损伤、神经功能缺损、小胶质细胞/巨噬细胞活化和脑白细胞浸润的影响、Western印迹、聚合酶链反应和流式细胞术。组织化学研究表明，TnC 在包含梗塞核心的缺血性纹状体中重新表达，并与 Iba1+ 小胶质细胞/巨噬细胞积累最强的区域重叠。TnC 缺乏增加了病灶周围皮层的整体 Iba1 免疫反应性，表明 TnC 可能会限制小胶质细胞向梗死核心的分布。通过在 3D 中分析小胶质细胞形态，我们发现与野生型小鼠相比，TnC 缺陷的大脑中缺血后 3 天和 7 天小胶质细胞区域、分支和体积的损失被放大。小胶质细胞数量在基因型之间没有差异。因此，TnC 缺乏减少了小胶质细胞对组织的监视。与此同时，与野生型小鼠相比，TnC 缺陷的缺血性脑实质中浸润的白细胞数量，更具体地说是 T 细胞数量增加。缺血性损伤和神经功能缺损不受 TnC 缺乏的影响。我们提出，TnC 缺陷小鼠中小胶质细胞监测的减少可能有利于缺血性脑中的白细胞积累。