Davies S J, Fitch M T, Memberg S P, Hall A K, Raisman G, Silver J
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Nature. 1997;390(6661):680-3. doi: 10.1038/37776.
It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.
人们普遍认为，成年哺乳动物的中枢神经系统（CNS）无法再生轴突。除了损伤部位胶质瘢痕形成所带来的物理或分子屏障外，还有观点认为正常的有髓鞘中枢神经系统环境含有强大的生长抑制剂或缺乏促进生长的分子。在这里，我们通过使用一种将瘢痕形成降至最低的微移植技术，将微量解离的成年大鼠背根神经节直接注射到成年大鼠中枢神经系统通路中，来研究在没有胶质瘢痕形成的情况下，成年中枢神经系统白质是否能够支持成年轴突的长距离再生。这种无创伤的注射程序使大量再生的成年轴突能够直接接触宿主胶质区域，我们发现它们在白质中迅速延伸很长距离，最终侵入灰质。再生失败与移植界面细胞外基质中蛋白聚糖水平的升高精确相关，而成功再生的移植则与这些分子的最小上调相关。据我们所知，我们的结果首次证明，损伤部位的反应性胶质细胞外基质与体内轴突再生失败直接相关，并且胶质瘢痕以外的成年有髓白质束对再生具有高度的容许性。
