Shifman M I, Zhang G, Selzer M E
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Comp Neurol. 2008 Sep 20;510(3):269-82. doi: 10.1002/cne.21789.
There is controversy about whether axotomized neurons undergo death or only severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from complete spinal transection, but only about half of the severed spinal-projecting axons regenerate through the site of injury. The fates of the unregenerated neurons remain unknown, and until now death of axotomized spinal-projecting neurons has not been described in the lamprey brain. We now report that in animals allowed to survive for 12 or more weeks after spinal cord transection, several identified reticulospinal (RS) neurons were missing in Nissl-stained or neurofilament-immunostained brain whole mounts. At earlier times, these neurons were swollen and pale in Nissl-stained preparations. Retrograde fluorescent labeling from the site of transection combined with TUNEL histochemistry suggested that neuronal death, including that of the identified RS neurons, began in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not seen in untransected animals. The TUNEL positivity suggests that some cells were dying by apoptosis. Of special interest, among the identified neurons, this delayed cell death was restricted to neurons that at earlier posttransection times have a low probability of regeneration. These data show that SCI induces delayed cell death in lamprey spinal-projecting neurons and suggest that the reason why some neurons are "bad regenerators" is that they are already undergoing apoptotic cell death. Thus protection from apoptosis may be necessary in order to enhance axonal regeneration after SCI.
对于哺乳动物脊髓损伤（SCI）后，轴突被切断的神经元是会死亡还是仅发生严重萎缩，存在争议。七鳃鳗能从完全性脊髓横断中恢复，但只有约一半被切断的脊髓投射轴突能通过损伤部位再生。未再生神经元的命运尚不清楚，而且迄今为止，七鳃鳗脑中轴突被切断的脊髓投射神经元的死亡情况尚未见报道。我们现在报告，在脊髓横断后存活12周或更长时间的动物中，在尼氏染色或神经丝免疫染色的脑整体标本中，几个已确定的网状脊髓（RS）神经元缺失。在更早的时候，这些神经元在尼氏染色标本中肿胀且颜色变淡。从横断部位进行的逆行荧光标记结合TUNEL组织化学表明，包括已确定的RS神经元在内的神经元死亡在横断后4周的动物中开始，在12 - 16周达到高峰。在未横断的动物中未观察到这种情况。TUNEL阳性表明一些细胞正在通过凋亡死亡。特别有趣的是，在已确定的神经元中，这种延迟性细胞死亡仅限于在横断后早期再生概率较低的神经元。这些数据表明，SCI会诱导七鳃鳗脊髓投射神经元的延迟性细胞死亡，并表明一些神经元是“不良再生者”的原因是它们已经在经历凋亡性细胞死亡。因此，为了增强SCI后的轴突再生，可能有必要防止细胞凋亡。
