Regeneration of adult axons in white matter tracts of the central nervous system
Regeneration of adult axons in white matter tracts of the central nervous system
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DOI：
10.1038/37776
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发表时间：
1997-12-25
期刊：
影响因子：
64.8
通讯作者：
Silver, J
中科院分区：
文献类型：
--
作者：
Davies, SJA;Fitch, MT;Silver, J
人们普遍认为成年哺乳动物中枢神经系统（CNS）不能再生轴突（1），除了病变部位神经胶质瘢痕形成的物理或分子屏障（2-4）外，已表明正常的有髓鞘CNS环境含有有效的生长抑制剂（5，6）或缺乏生长促进分子（1，7）。在这里，我们研究了成年CNS白色物质是否可以在没有神经胶质瘢痕形成的情况下支持成年轴突的长距离再生，通过使用显微移植技术（8）将微小体积的分离的成年大鼠背根神经节直接注射到成年大鼠CNS通路中，以最大限度地减少瘢痕形成（9）。这种无创伤的注射过程允许相当数量的再生成年轴突立即进入宿主神经胶质区，我们发现它们在白色物质中迅速延伸很长一段距离，最终侵入灰质。流产再生与移植界面细胞外基质中蛋白多糖水平的增加精确相关，而成功再生的移植物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，并且胶质疤痕之外的成人有髓鞘的白色物质束可以高度允许再生。
It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons(1), In addition to physical or molecular barriers presented by glial scarring at the lesion site(2-4), it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors(5,6) or lacks growth-promoting molecules(1,7). 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(8) that minimizes scarring(9) 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.