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首页> 外文期刊>Journal of neuroinflammation >Inhibition of astroglial NF-kappaB enhances oligodendrogenesis following spinal cord injury
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Inhibition of astroglial NF-kappaB enhances oligodendrogenesis following spinal cord injury

机译：星形胶质细胞NF-κB的抑制作用增强脊髓损伤后的少突胶质生成

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Background Astrocytes are taking the center stage in neurotrauma and neurological diseases as they appear to play a dominant role in the inflammatory processes associated with these conditions. Previously, we reported that inhibiting NF-κB activation in astrocytes, using a transgenic mouse model (GFAP-IκBα-dn mice), results in improved functional recovery, increased white matter preservation and axonal sparing following spinal cord injury (SCI). In the present study, we sought to determine whether this improvement, due to inhibiting NF-κB activation in astrocytes, could be the result of enhanced oligodendrogenesis in our transgenic mice. Methods To assess oligodendrogenesis in GFAP-IκBα-dn compared to wild-type (WT) littermate mice following SCI, we used bromodeoxyuridine labeling along with cell-specific immuno-histochemistry, confocal microscopy and quantitative cell counts. To further gain insight into the underlying molecular mechanisms leading to increased white matter, we performed a microarray analysis in na?ve and 3 days, 3 and 6 weeks following SCI in GFAP-IκBα-dn and WT littermate mice. Results Inhibition of astroglial NF-κB in GFAP-IκBα-dn mice resulted in enhanced oligodendrogenesis 6 weeks following SCI and was associated with increased levels of myelin proteolipid protein compared to spinal cord injured WT mice. The microarray data showed a large number of differentially expressed genes involved in inflammatory and immune response between WT and transgenic mice. We did not find any difference in the number of microglia/leukocytes infiltrating the spinal cord but did find differences in their level of expression of toll-like receptor 4. We also found increased expression of the chemokine receptor CXCR4 on oligodendrocyte progenitor cells and mature oligodendrocytes in the transgenic mice. Finally TNF receptor 2 levels were significantly higher in the transgenic mice compared to WT following injury. Conclusions These studies suggest that one of the beneficial roles of blocking NF-κB in astrocytes is to promote oligodendrogenesis through alteration of the inflammatory environment.
机译：背景星形胶质细胞在神经创伤和神经系统疾病中处于中心地位，因为它们似乎在与这些疾病相关的炎症过程中起主导作用。先前，我们报道了使用转基因小鼠模型（GFAP-IκBα-dn小鼠）抑制星形胶质细胞中NF-κB活化，可改善功能恢复，增加脊髓损伤（SCI）后白质的保存和减少轴突损伤。在本研究中，我们试图确定这种改善是否是由于抑制星形胶质细胞中NF-κB的活化所致，而这可能是我们转基因小鼠中少突胶质生成的结果。方法为了评估SCI后与野生型（WT）同窝小鼠相比GFAP-IκBα-dn的少突胶质形成，我们使用了溴脱氧尿苷标记以及细胞特异性免疫组化，共聚焦显微镜和定量细胞计数。为了进一步了解导致白质增加的潜在分子机制，我们在GFAP-IκBα-dn和WT同窝仔小鼠的SCI后的中午和第3天，3、3和6周进行了微阵列分析。结果GFAP-IκBα-dn小鼠中星形胶质细胞NF-κB的抑制导致SCI 6周后少突胶质生成的增强，并且与脊髓损伤的WT小鼠相比，髓磷脂蛋白脂质蛋白的水平增加。微阵列数据显示，大量差异表达的基因参与了野生型和转基因小鼠之间的炎症和免疫反应。我们没有发现浸润脊髓的小胶质细胞/白细胞数目有任何差异，但是确实发现了它们的toll样受体4表达水平存在差异。我们还发现趋化因子受体CXCR4在少突胶质祖细胞和成熟少突胶质细胞中的表达增加。在转基因小鼠中。最后，与损伤后的WT相比，转基因小鼠中的TNF受体2水平显着更高。结论这些研究表明，阻断星形胶质细胞中NF-κB的有益作用之一是通过改变炎症环境来促进少突胶质生成。

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