Tomita Koichi, Hata Yuki, Kubo Tateki, Fujiwara Toshihiro, Yano Kenji, Hosokawa Ko
Department of Plastic Surgery, Osaka University, Graduate School of Medicine, 2-2 C11 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Neurosci Lett. 2009 Sep 11;461(1):36-40. doi: 10.1016/j.neulet.2009.05.075. Epub 2009 Jun 9.
In peripheral nerve transection injury, continuity of axons as well as that of the basal lamina is disconnected. In such case, migrating Schwann cells (SCs) would be the only axonal guidance at an early stage of regeneration. However, it takes a few days for the dedifferentiated SCs to start migration, while axonal growth begins a few hours after injury. Consequently, the axons without guidance extensively branch out and wander off at the lesion, resulting in aberrant reinnervation. Therefore, enhancing SCs migration could be an attractive therapeutic strategy. In this study, we investigated the effects of the in vivo nerve predegeneration on SC migration and the time course of these changes. In our analysis, we established a novel animal model by nerve transplantation from S100-GFP mice (in which SCs constitutively express green fluorescent protein driven by the S100B promoter), by which SC migration could be exclusively visualized. Our results showed that SCs acquire the maximal migration ability with 14-day predegeneration, but subsequently it gradually decreased. There was a correlation between the time course of the changes in SC migration and the number of activated macrophages. These findings suggest that using predegenerated nerve grafts in repairing the transected nerves could facilitate SC migration into the recipient nerve stump. This technique could be beneficial for early establishment of axonal guidance and possible functional improvement after transection injury.
在周围神经横断损伤中，轴突以及基膜的连续性均被切断。在这种情况下，迁移的雪旺细胞（SCs）将是再生早期唯一的轴突导向。然而，去分化的SCs需要几天时间才开始迁移，而轴突生长在损伤后几小时就开始了。因此，没有导向的轴突在损伤处广泛分支并游走，导致异常再支配。所以，增强SCs迁移可能是一种有吸引力的治疗策略。在本研究中，我们研究了体内神经预变性对SCs迁移的影响以及这些变化的时间进程。在我们的分析中，我们通过从S100-GFP小鼠（其中SCs组成性表达由S100B启动子驱动的绿色荧光蛋白）进行神经移植建立了一种新型动物模型，通过该模型可以专门观察到SCs迁移。我们的结果表明，SCs在预变性14天时获得最大迁移能力，但随后逐渐下降。SCs迁移变化的时间进程与活化巨噬细胞的数量之间存在相关性。这些发现表明，在修复横断神经时使用预变性神经移植物可以促进SCs迁移到受体神经残端。该技术可能有利于轴突导向的早期建立以及横断损伤后可能的功能改善。
