Shuman S L, Bresnahan J C, Beattie M S
Neuroscience Graduate Studies Program, The Ohio State University, Columbus, USA.
J Neurosci Res. 1997 Dec 1;50(5):798-808. doi: 10.1002/(SICI)1097-4547(19971201)50:5<798::AID-JNR16>3.0.CO;2-Y.
Following spinal cord contusion in the rat, apoptosis has been observed in the white matter for long distances remote from the center of the lesion and is primarily associated with degenerating fiber tracts. We have previously reported that many of the apoptotic cells are oligodendrocytes. Here we show that the oligodendrocyte death is maximal at 8 days postinjury and suggest that loss of oligodendrocytes may result in demyelination of axons that have survived the initial trauma. There are two mechanisms that may account for the observed oligodendrocyte apoptosis. The apoptotic cell death may result from the loss of trophic support after axonal degeneration or it may be the consequence of microglial activation. The hypothesis that oligodendrocyte apoptosis is secondary to microglial activation is supported by our observations of microglia with an activated morphology in the same regions as apoptosis and apparent contact between some of the apoptotic oligodendrocytes and microglial processes. In addition to oligodendrocyte apoptosis, a subpopulation of microglia appears to be susceptible to apoptotic cell death as well, as evidenced by the presence of apoptotic bodies in OX42 immunopositive profiles. Thus, the population of apoptotic cells following spinal cord contusion is comprised of oligodendrocytes and putative phagocytic microglia or macrophages. Given the delayed time course of oligodendrocyte death, the apoptotic death of oligodendrocytes may be amenable to pharmacological intervention with subsequent improvement in functional recovery.
大鼠脊髓挫伤后，在远离损伤中心的长距离白质中观察到凋亡现象，且主要与退变的纤维束相关。我们之前报道过，许多凋亡细胞是少突胶质细胞。在此我们表明，少突胶质细胞死亡在损伤后8天达到峰值，并提示少突胶质细胞的丢失可能导致在初始创伤中存活下来的轴突脱髓鞘。有两种机制可能解释所观察到的少突胶质细胞凋亡。凋亡性细胞死亡可能是轴突退变后营养支持丧失所致，也可能是小胶质细胞激活的结果。少突胶质细胞凋亡继发于小胶质细胞激活这一假说得到了我们的观察结果支持，即在与凋亡相同的区域观察到具有激活形态的小胶质细胞，并且一些凋亡的少突胶质细胞与小胶质细胞突起之间存在明显接触。除了少突胶质细胞凋亡外，小胶质细胞的一个亚群似乎也易发生凋亡性细胞死亡，OX42免疫阳性细胞中存在凋亡小体就证明了这一点。因此，脊髓挫伤后的凋亡细胞群体由少突胶质细胞以及假定的吞噬性小胶质细胞或巨噬细胞组成。鉴于少突胶质细胞死亡的时间进程延迟，少突胶质细胞的凋亡性死亡可能适合进行药物干预，从而随后改善功能恢复。
