Oudega M, Xu X M, Guénard V, Kleitman N, Bunge M B
Chambers Family Electron Microscopy Laboratory, University of Miami School of Medicine, FL 33136, USA.
Glia. 1997 Mar;19(3):247-58. doi: 10.1002/(sici)1098-1136(199703)19:3<247::aid-glia7>3.0.co;2-w.
Insulin-like growth factor-I (IGF-I) promotes axonal regeneration in the peripheral nervous system and this effect is enhanced by platelet-derived growth factor (PDGF). We decided, therefore, to study the effects of these factors on axonal regeneration in the adult rat spinal cord. Semipermeable polymer tubes, closed at the distal end, containing Matrigel mixed with cultured rat Schwann cells and IGF-I/PDGF, were placed at the proximal stump of the spinal cord after removal of the thoracic T9-11 segments. Control animals received implants of only Matrigel and Schwann cells or only Matrigel and IGF-I/PDGF. Four weeks after implantation, electron microscopic analysis showed that the addition of IGF-I/PDGF resulted in an increase in the myelinated:unmyelinated fiber ratio from 1:7 to 1:3 at 3 mm in the Schwann cell graft, and that myelin sheath thickness was increased 2-fold. The reduced number of unmyelinated axons was striking in electron micrographs. These results suggested that IGF-I/PDGF enhanced myelin formation of regenerated axons in Schwann cell implants, but there was a 36% decrease in the total number of myelinated axons at the 3 mm level of the graft. This finding and the altered myelinated:unmyelinated fiber ratio revealed that the overall fiber regeneration into Schwann cell implants was diminished up to 63% by IGF-I/PDGF. Histological evaluation revealed that there were more larger cavities in tissue at the proximal spinal cord-graft interface in animals receiving a Schwann cell implant with IGF-I/PDGF. Such cavitation might have contributed to the reduction in axonal ingrowth. In sum, the results indicate that whereas the combination of IGF-I and PDGF enhances myelination of regenerating spinal cord axons entering implants of Matrigel and Schwann cells after midthoracic transection, the overall regeneration of axons into such Schwann cell grafts is diminished.
胰岛素样生长因子-I（IGF-I）可促进周围神经系统中的轴突再生，血小板衍生生长因子（PDGF）可增强这种作用。因此，我们决定研究这些因子对成年大鼠脊髓轴突再生的影响。在切除胸段T9 - 11节段后，将封闭远端的半透性聚合物管置于脊髓近端残端，管内含有与培养的大鼠雪旺细胞及IGF-I/PDGF混合的基质胶。对照动物植入的仅是基质胶和雪旺细胞，或仅是基质胶和IGF-I/PDGF。植入四周后，电子显微镜分析显示，添加IGF-I/PDGF可使雪旺细胞移植物中3 mm处有髓纤维与无髓纤维的比例从1:7增加到1:3，并且髓鞘厚度增加了两倍。电子显微镜照片中无髓轴突数量的减少十分显著。这些结果表明，IGF-I/PDGF可增强雪旺细胞移植物中再生轴突的髓鞘形成，但在移植物3 mm水平处有髓轴突的总数减少了36%。这一发现以及有髓与无髓纤维比例的改变表明，IGF-I/PDGF使进入雪旺细胞移植物的总体纤维再生减少了多达63%。组织学评估显示，在接受含IGF-I/PDGF的雪旺细胞移植物的动物中，脊髓近端移植物界面处的组织中有更多更大的空洞。这种空洞化可能导致了轴突向内生长的减少。总之，结果表明，虽然IGF-I和PDGF的组合可增强胸段中段横断后进入基质胶和雪旺细胞移植物的脊髓再生轴突的髓鞘形成，但轴突向这种雪旺细胞移植物的总体再生却减少了。
