Kalderon N, Alfieri A A, Fuks Z
Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):10058-62. doi: 10.1073/pnas.87.24.10058.
We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.
我们研究了临床剂量水平的X射线辐射调控细胞成分的潜力,进而改变成年哺乳动物中枢神经组织(大鼠嗅球)横断损伤后果的可能性。若在损伤后的特定时间窗内进行辐射,可使切口处反应性星形胶质细胞减少或消失。在消除胶质增生的最佳条件下(损伤后15 - 18天),对切断的嗅球进行辐射可避免损伤的一些退行性后果。我们观察到,辐射伴随着损伤部位周围组织退变的预防、典型细胞分层得以维持的结构愈合以及一些被切断轴突的二尖瓣细胞(嗅球主要神经元)的挽救。因此,辐射导致正常组织形态部分得以保留。据推测,损伤会引发侵入性细胞群的产生,反应性星形胶质细胞就是其中之一。我们的结果表明,通过辐射选择性消除这些细胞能使一些完全恢复所必需的再生过程得以持续进行。文中讨论了这些细胞的细胞靶点、它们在恢复过程中的干预方式以及辐射作为损伤中枢神经系统治疗手段的潜在作用。