Granulocyte-macrophage colony-stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush
Granulocyte-macrophage colony-stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush
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DOI：
10.1111/ejn.14106
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发表时间：
2018-09-01
影响因子：
3.4
通讯作者：
Rodrigues de Oliveira, Alexandre Leite
中科院分区：
文献类型：
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作者：
Bombeiro, Andre Luis;Nunes Pereira, Bruna Toledo;Rodrigues de Oliveira, Alexandre Leite
周围神经损伤严重损害患者的生活质量，因为很少能完全康复。轴突破坏后，远端神经残端发生碎裂，髓磷脂分解；随后的再生进展取决于细胞碎片的清除。除了组织清除之外，巨噬细胞还释放有助于轴突生长的血管生成和神经营养因子。基于巨噬细胞对神经再生的重要性，特别是在对损伤的最初反应期间，我们在坐骨神经压碎后以不同的时间间隔用粒细胞巨噬细胞集落刺激因子（GM-CSF）治疗小鼠。在损伤后的不同时间间隔对坐骨神经进行组织学分析，以确定巨噬细胞的存在和再生指标。功能恢复后进行自动步行道测试。我们发现 GM-CSF 增强了早期轴突生长，损伤后 7 天生长相关蛋白的表达增强表明了这一点。诱导性一氧化氮合酶表达在再生过程开始和结束时增加，表明一氧化氮参与轴突生长和修剪。正如预期的那样，GM-CSF 治疗刺激了巨噬细胞浸润，并在第 7 天和第 14 天时增加；然而，它并没有改善髓磷脂清除率。相反，GM-CSF 刺激早期脑源性神经营养因子 (BDNF) 的产生，并在 7 天时达到峰值。 GM-CSF 治疗并未改善运动恢复模式。目前的结果表明 GM-CSF 可能对早期轴突再生具有有益的作用。
Peripheral nerve injuries severely impair patients' quality of life as full recovery is seldom achieved. Upon axonal disruption, the distal nerve stump undergoes fragmentation, and myelin breaks down; the subsequent regeneration progression is dependent on cell debris removal. In addition to tissue clearance, macrophages release angiogenic and neurotrophic factors that contribute to axon growth. Based on the importance of macrophages for nerve regeneration, especially during the initial response to injury, we treated mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) at various intervals after sciatic nerve crushing. Sciatic nerves were histologically analyzed at different time intervals after injury for the presence of macrophages and indicators of regeneration. Functional recovery was followed by an automated walking track test. We found that GM-CSF potentiated early axon growth, as indicated by the enhanced expression of growth-associated protein at 7days postinjury. Inducible nitric oxide synthase expression increased at the beginning and at the end of the regenerative process, suggesting that nitric oxide is involved in axon growth and pruning. As expected, GM-CSF treatment stimulated macrophage infiltration, which increased at 7 and 14days; however, it did not improve myelin clearance. Instead, GM-CSF stimulated early brain-derived neurotrophic factor (BDNF) production, which peaked at 7days. Locomotor recovery pattern was not improved by GM-CSF treatment. The present results suggest that GM-CSF may have beneficial effects on early axonal regeneration.