Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge
Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge
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DOI：
10.1006/mcne.2002.1185
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发表时间：
2002-11-01
影响因子：
3.5
通讯作者：
Howells, DW
中科院分区：
文献类型：
--
作者：
Batchelor, PE;Porritt, MJ;Howells, DW
在哺乳动物CNS损伤后，轴突在伤口边缘附近发芽。然后生长停止，轴突无法穿过病变部位。在这项研究中，使用多巴胺能发芽在受伤的纹状体作为一个模型系统，我们已经研究了创伤周围发芽纤维反应性胶质细胞和巨噬细胞的关系。在受伤后的第一周，我们发现发芽的纤维与激活的小胶质细胞形成密切的关系，因为它们向伤口边缘移动。一旦到达伤口边缘，在单个巨噬细胞周围形成复杂的纤维丛。然而，轴突未能进一步生长到伤口内部，尽管在该位置存在许多巨噬细胞。我们发现，随着伤口边缘的接近，激活的小胶质细胞表达的BDNF逐渐增加，而巨噬细胞表达的GDNF在伤口边缘最高。相比之下，这两种因子的表达在伤口的巨噬细胞填充的内部内显著减少。我们的数据表明，伤口周围发芽纤维生长向伤口边缘沿着逐渐增加的营养梯度产生的小胶质细胞和巨噬细胞活化。一旦在伤口边缘，在最大神经营养因子表达点处，巨噬细胞上的发芽停止，并且进一步轴突生长到伤口核心的相对较差的营养环境中未能发生。
Following injury to the mammalian CNS, axons sprout in the vicinity of the wound margin. Growth then ceases and axons fail to cross the lesion site. In this study, using dopaminergic sprouting in the injured striatum as a model system, we have examined the relationship of periwound sprouting fibers to reactive glia and macrophages. In the first week after injury we find that sprouting fibers form intimate relationships with activated microglia as they traverse toward the wound edge. Once at the wound edge, complicated plexuses of fibers form around individual macrophages. Axons, however, fail to grow further into the interior of the wound despite the presence of many macrophages in this location. We find that the expression of BDNF by activated microglia progressively increases as the wound edge is approached, while GDNF expression by macrophages is highest at the immediate wound margin. In contrast, the expression of both factors is substantially reduced within the macrophage-filled interior of the wound. Our data suggest that periwound sprouting fibers grow toward the wound margin along an increasing trophic gradient generated by progressively microglial and macrophage activation. Once at the wound edge, sprouting ceases over macrophages at the point of maximal neurotrophic factor expression and further axonal growth into the relatively poor trophic environment of the wound core fails to occur.