Analysis of Schwann Cell Migration and Axon Regeneration Following Nerve Injury in the Sciatic Nerve Bridge
Analysis of Schwann Cell Migration and Axon Regeneration Following Nerve Injury in the Sciatic Nerve Bridge
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DOI：
10.3389/fnmol.2019.00308
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发表时间：
2019-12-10
影响因子：
4.8
通讯作者：
Dun, Xin-peng
中科院分区：
文献类型：
--
作者：
Chen, Bing;Chen, Quan;Dun, Xin-peng
尽管雪旺细胞和轴突之间的相互作用是神经再生成功的关键，但雪旺细胞在横断损伤后迁移到神经间隙中的行为以及迁移的雪旺细胞如何与神经桥内再生的轴突相互作用尚未被详细研究。在这项研究中，我们结合使用我们的整体坐骨神经染色和使用蛋白脂蛋白-绿色荧光蛋白(PLP-GFP)小鼠模型来标记雪旺细胞，并检测了神经横断损伤后雪旺细胞和再生轴突在坐骨神经间隙中的迁移行为。我们在这里表明，雪旺细胞从两个神经残端开始迁移的时间晚于从近端神经残端再生轴突的时间。小鼠坐骨神经横断伤后4d才能观察到第一批迁移的雪旺细胞。损伤后第5天，雪旺细胞从近端神经残端迁徙超过再生轴突，7天时在神经桥体内形成雪旺细胞索。再生轴突在第6天开始附着在迁移中的雪旺细胞上，然后沿着它们的轨迹穿过神经间隙。我们还观察到神经桥中的雪旺细胞索不够宽，不足以引导所有再生轴突穿过神经桥，导致再生轴突沿着近端和远端神经残端的外部生长。从这一分析中，我们证明了雪旺细胞在控制神经间隙中轴突再生的方向性和速度方面起着至关重要的作用。我们还证明，利用PLP-GFP小鼠模型标记雪旺细胞，并结合坐骨神经轴突全染色技术，是研究周围神经再生过程的有用的研究模型。
While it is proposed that interaction between Schwann cells and axons is key for successful nerve regeneration, the behavior of Schwann cells migrating into a nerve gap following a transection injury and how migrating Schwann cells interact with regenerating axons within the nerve bridge has not been studied in detail. In this study, we combine the use of our whole-mount sciatic nerve staining with the use of a proteolipid protein-green fluorescent protein (PLP-GFP) mouse model to mark Schwann cells and have examined the behavior of migrating Schwann cells and regenerating axons in the sciatic nerve gap following a nerve transection injury. We show here that Schwann cell migration from both nerve stumps starts later than the regrowth of axons from the proximal nerve stump. The first migrating Schwann cells are only observed 4 days following mouse sciatic nerve transection injury. Schwann cells migrating from the proximal nerve stump overtake regenerating axons on day 5 and form Schwann cell cords within the nerve bridge by 7 days post-transection injury. Regenerating axons begin to attach to migrating Schwann cells on day 6 and then follow their trajectory navigating across the nerve gap. We also observe that Schwann cell cords in the nerve bridge are not wide enough to guide all the regenerating axons across the nerve bridge, resulting in regenerating axons growing along the outside of both proximal and distal nerve stumps. From this analysis, we demonstrate that Schwann cells play a crucial role in controlling the directionality and speed of axon regeneration across the nerve gap. We also demonstrate that the use of the PLP-GFP mouse model labeling Schwann cells together with the whole sciatic nerve axon staining technique is a useful research model to study the process of peripheral nerve regeneration.