Davies S J, Field P M, Raisman G
The Division of Neurobiology, National Institute for Medical Research, MRC, London, United Kingdom.
Exp Neurol. 1996 Dec;142(2):203-16. doi: 10.1006/exnr.1996.0192.
The present study tests whether lesions small enough to allow the rapid reestablishment of a normally aligned tract glial framework would provide a permissive environment for the regeneration of cut adult CNS axons. We made penetrating microlesions which cut a narrow beam of axons in the adult rat cingulum, but caused minimal damage to the tract glial framework and no cavitation. The proximal tips of cut axons were identified by enhanced immunoreactivity for low affinity neurotrophin receptor, p75. From 1 day they became expanded into large growth-cone-like structures. At later times some axons turned back and extended in the reverse direction. Up to 14 days (after which time p75 could no longer be used as a marker), no axons advanced beyond the line of the lesion. From 1 to 2 days, OX42 immunostaining and electron microscopy showed that the lesion site was densely infiltrated by macrophages, which disappeared by 3 to 4 days. This was followed by a local hypertrophy of the OX42 immunoreactive resident tract microglial cells and an increase in both GFAP and vimentin immunoreactivity of the tract astrocytes. These responses were greatly reduced by 8 days, when the longitudinal alignment of glial processes across the lesion site was similar to that of an undamaged tract. The large growth-cone-like structures formed at the ends of the cut axons resemble those of developing axons exposed to chemorepulsive factors. This suggests that cellular elements in adult tract lesions may also exert chemorepulsive influences blocking regeneration of axons even in an apparently "open" tract framework.
本研究旨在测试小到足以使正常排列的束状胶质框架快速重建的损伤是否能为成年中枢神经系统（CNS）轴突切断后的再生提供适宜环境。我们制作了穿透性微损伤，切断成年大鼠扣带束中的一束狭窄轴突束，但对束状胶质框架造成的损伤最小且未形成空洞。通过增强对低亲和力神经营养因子受体p75的免疫反应性来识别切断轴突的近端末梢。从第1天起，它们扩展成大的生长锥样结构。在随后的时间里，一些轴突折返并向相反方向延伸。直至14天（此后p75不能再用作标记物），没有轴突越过损伤线向前延伸。在1至2天，OX42免疫染色和电子显微镜显示损伤部位被巨噬细胞密集浸润，这些巨噬细胞在3至4天消失。随后，OX42免疫反应性的驻留束状小胶质细胞出现局部肥大，束状星形胶质细胞的GFAP和波形蛋白免疫反应性均增加。到第8天时，这些反应大大减弱，此时穿过损伤部位的胶质突起的纵向排列与未损伤束的排列相似。在切断轴突末端形成的大的生长锥样结构类似于暴露于化学排斥因子的发育中轴突的结构。这表明成年束状损伤中的细胞成分也可能施加化学排斥影响，即使在明显“开放”的束状框架中也会阻碍轴突再生。
