Houle J D, Ziegler M K
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
J Neural Transplant Plast. 1994 Apr-Jun;5(2):115-24. doi: 10.1155/NP.1994.115.
The ability of a substrate bound neurotrophic factor to promote growth of ascending sensory axons across a complete transection lesion of the rat spinal cord was examined in a transplantation model. Aspiration lesions created a 3 mm long cavity in the upper lumbar spinal cord of adult rats. Five weeks after injury two strips of nerve growth factor-treated nitrocellulose were implanted, each in a medio-lateral position, and apposed to the rostral and caudal surfaces of the cavity. Control animals received untreated nitrocellulose implants. Fetal spinal cord tissue was transplanted alongside and between these strips. Six weeks post transplantation, animals were sacrificed and vibratome sections through the grafts were processed for immunocytochemical demonstration of ingrowing axons expressing calcitonin gene-related peptide (CGRP-IR). Immunolabeled axons were abundant at the caudal interface between host tissue and the NGF-treated nitrocellulose implants, with dense fascicles of fibers abutting the grafts. As the distance from the caudal surface increased some CGRP-IR fibers extended into the fetal tissue although most appeared to remain oriented in a longitudinal course adjacent to the nitrocellulose. Labeled axons were evident along the entire length of the nitrocellulose and appeared to aggregate at the rostral tip of the implant, with many fibers extending into the host spinal cord rostral to the lesion/transplant site. When untreated nitrocellulose was implanted, fewer labeled axons appeared to extend beyond the caudal host-graft interface. Most CGRP-IR axons displayed limited association or contact with the untreated nitrocellulose in this condition. Computer-assisted quantitative analysis indicated that NGF-treated nitrocellulose supported regrowing host axons for nearly three times the length exhibited by axons associated with non-treated nitrocellulose implants. These results indicate that substrate bound nerve growth factor has the capacity to enhance the regrowth of ascending sensory axons across a traumatic spinal cord injury site. The potential to reestablish functional contacts across such a lesion may be heightened by the ability of neurotrophic factors to promote more extensive axonal regrowth.
在一个移植模型中，研究了结合在底物上的神经营养因子促进大鼠脊髓完全横断损伤后上行感觉轴突生长的能力。通过抽吸损伤在成年大鼠上腰段脊髓制造一个3毫米长的空洞。损伤后5周，植入两条经神经生长因子处理的硝酸纤维素条带，每条位于中外侧位置，贴附于空洞的头端和尾端表面。对照动物植入未经处理的硝酸纤维素。将胎儿脊髓组织移植到这些条带旁边和之间。移植后6周，处死动物，对通过移植物的振动切片进行处理，用于免疫细胞化学显示表达降钙素基因相关肽（CGRP-IR）的长入轴突。在宿主组织与经NGF处理的硝酸纤维素植入物之间的尾端界面处，免疫标记的轴突丰富，有密集的纤维束紧靠移植物。随着距尾端表面距离的增加，一些CGRP-IR纤维延伸到胎儿组织中，尽管大多数似乎仍沿与硝酸纤维素相邻的纵向走行。标记的轴突在硝酸纤维素的整个长度上都很明显，并且似乎聚集在植入物头端的尖端，许多纤维延伸到损伤/移植部位头端的宿主脊髓中。当植入未经处理的硝酸纤维素时，似乎很少有标记的轴突延伸到尾端宿主-移植物界面之外。在这种情况下，大多数CGRP-IR轴突与未经处理的硝酸纤维素的关联或接触有限。计算机辅助定量分析表明，经NGF处理的硝酸纤维素支持宿主再生轴突的长度几乎是与未经处理的硝酸纤维素植入物相关的轴突所显示长度的三倍。这些结果表明，结合在底物上的神经生长因子有能力增强上行感觉轴突穿过创伤性脊髓损伤部位的再生。神经营养因子促进更广泛轴突再生的能力可能会提高跨越此类损伤重新建立功能联系的潜力。
