Ramón-Cueto A, Plant G W, Avila J, Bunge M B
The Chambers Family Electron Microscopy Laboratory, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33101, USA.
J Neurosci. 1998 May 15;18(10):3803-15. doi: 10.1523/JNEUROSCI.18-10-03803.1998.
The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional impairment. To induce axonal regeneration in the transected adult rat spinal cord, we have used the axonal growth-promoting properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC)-filled guidance channels were grafted to bridge both cord stumps, and suspensions of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline of both stumps, 1 mm from the edges of the channel. In EG-transplanted animals, numerous neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-, and serotonin-immunoreactive fibers traversed the glial scars formed at both cord-graft interfaces. Supraspinal serotonergic axons crossed the transection gap through connective tissue bridges formed on the exterior of the channels, avoiding the channel interior. Strikingly, after crossing the distal glial scar, these fibers elongated in white and periaqueductal gray matter, reaching the farthest distance analyzed (1.5 cm). Tracer-labeled axons present in SC grafts were found to extend across the distal interface and up to 800 microm beyond in the distal cord. Long-distance regeneration (at least 2.5 cm) of injured ascending propriospinal axons was observed in the rostral spinal cord. Transplanted EG migrated longitudinally and laterally from the injection sites, reaching the farthest distance analyzed (1.5 cm). They moved through white matter tracts, gray matter, and glial scars, overcoming the inhibitory nature of the CNS environment, and invaded SC and connective tissue bridges and the dorsal and ventral roots adjacent to the transection site. Transplanted EG and regenerating axons were found in the same locations. Because EG seem to provide injured spinal axons with appropriate factors for long-distance elongation, these cells offer new possibilities for treatment of CNS conditions that require axonal regeneration.
成年哺乳动物脊髓损伤后轴突再生的缺乏会导致永久性功能障碍。为了诱导成年大鼠横断脊髓的轴突再生，我们利用了成年嗅球被膜胶质细胞（EG）促进轴突生长的特性。将充满雪旺细胞（SC）的引导通道移植到脊髓两端以连接断端，并将纯度为98%的Hoechst标记的EG悬浮液立体定向注射到两端断端距通道边缘1毫米处的中线。在接受EG移植的动物中，许多神经丝、生长相关蛋白-43（GAP-43）、抗降钙素基因相关肽（CGRP）和5-羟色胺免疫反应性纤维穿过在脊髓与移植体界面处形成的胶质瘢痕。脊髓上5-羟色胺能轴突通过在通道外部形成的结缔组织桥穿过横断间隙，避开通道内部。令人惊讶的是，在穿过远端胶质瘢痕后，这些纤维在白质和导水管周围灰质中伸长，达到分析的最远点（1.5厘米）。发现在SC移植物中的示踪剂标记轴突穿过远端界面并在远端脊髓中延伸800微米以上。在脊髓头端观察到损伤的上升性脊髓固有轴突的长距离再生（至少2.5厘米）。移植的EG从注射部位纵向和横向迁移，达到分析的最远点（1.5厘米）。它们穿过白质束、灰质和胶质瘢痕，克服中枢神经系统环境的抑制特性，并侵入SC和结缔组织桥以及横断部位附近的背根和腹根。在相同位置发现了移植的EG和再生轴突。由于EG似乎为损伤的脊髓轴突提供了长距离伸长的合适因子，这些细胞为治疗需要轴突再生的中枢神经系统疾病提供了新的可能性。
