Department of Physiology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
PLoS One. 2013 Apr 12;8(4):e61010. doi: 10.1371/journal.pone.0061010. Print 2013.
We examined the effects of gamma knife (GK) irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL) model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF), a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK irradiation of injured peripheral nerves may have beneficial effects.
我们使用大鼠部分坐骨神经结扎（PSL）模型研究了伽玛刀（GK）照射对受损神经的影响。在结扎后一周进行 GK 照射，并在结扎后三周进行神经准备。已知 GK 照射会在中枢神经系统中引起免疫反应，如胶质细胞激活。因此，我们使用免疫印迹和组织化学分析来确定 GK 照射对巨噬细胞的影响。与未照射的损伤神经相比，GK 处理的损伤神经中 Iba-1 蛋白（巨噬细胞标志物）的表达进一步增加。在 GK 照射的损伤坐骨神经中的 Iba-1 免疫组织化学研究表明，在结扎点远端区域，Iba-1 阳性巨噬细胞的积累得到增强。在同一区域，通过 GK 照射也更有效地清除髓鞘碎片。巨噬细胞清除髓鞘碎片被认为有助于轴突生长的许可环境。在免疫印迹研究中，GK 照射显著增加了 βIII-微管蛋白和髓鞘蛋白零的表达，它们分别是轴突再生和再髓鞘的标志物。甲苯胺蓝染色显示，在 GK 照射的损伤神经中，近端部位的再生纤维直径较大，而在远端部位的再生纤维数量增加。与未照射的损伤神经相比。这些结果表明，GK 照射损伤的神经促进了再生和再髓鞘。在行为研究中，在 PSL 大鼠中观察到 GK 照射可早期缓解痛觉过敏。当最初检测到 GK 诱导的痛觉过敏缓解时，通过 GK 照射，神经营养因子（GDNF）的表达显著增加，GDNF 是一种有效的镇痛因子。这些结果表明，GK 照射通过增加 GDNF 缓解痛觉过敏。这项研究提供了新的证据，表明 GK 照射损伤的周围神经可能具有有益的效果。
