Blesch Armin, Tuszynski Mark H
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
J Neurosci. 2007 Sep 26;27(39):10535-45. doi: 10.1523/JNEUROSCI.1903-07.2007.
Growth factors influence the topography of axonal projections during nervous system development and facilitate axonal sprouting and regeneration after injury in the adult. However, in the absence of target reinnervation and reestablishment of synaptic activity, we hypothesized that continuing delivery of neurotrophins would be required to sustain regenerating axons for prolonged times points after neurotrophin-induced axon growth after spinal cord injury (SCI) in the adult. Using tetracycline-inducible expression of brain-derived neurotrophic factor by genetically modified fibroblasts, we were able to extensively and significantly turn growth factor expression "on" or "off" in vitro and in vivo within sites of SCI. Notably, we find that transient growth factor delivery is sufficient to sustain regenerated axons for prolonged time periods within spinal cord lesion sites. Immunohistochemical analysis demonstrated an absence of neuronal targets or synapses within transient growth factor expressing grafts but the persistent presence of Schwann cells. Thus, the adult CNS appears capable of sustaining axons that have extended after transient growth factor delivery, an effect potentially attributable to the persistence of Schwann cells in lesion/graft sites.
生长因子在神经系统发育过程中影响轴突投射的拓扑结构，并在成体损伤后促进轴突发芽和再生。然而，在缺乏靶神经再支配和突触活动重建的情况下，我们推测，在成年脊髓损伤（SCI）后神经营养因子诱导轴突生长后，需要持续递送神经营养素来在延长的时间点维持再生轴突。利用基因改造的成纤维细胞对脑源性神经营养因子进行四环素诱导表达，我们能够在SCI部位在体外和体内广泛且显著地开启或关闭生长因子表达。值得注意的是，我们发现短暂递送生长因子足以在脊髓损伤部位将再生轴突维持较长时间。免疫组织化学分析表明，在短暂表达生长因子的移植物中不存在神经元靶标或突触，但施万细胞持续存在。因此，成年中枢神经系统似乎有能力维持在短暂递送生长因子后延伸的轴突，这种效应可能归因于损伤/移植物部位施万细胞的持续存在。
