Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
PLoS One. 2012;7(8):e43484. doi: 10.1371/journal.pone.0043484. Epub 2012 Aug 29.
It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury.
先前已经表明,脊髓损伤后,灰质的损失比白质的损失相对更快,这表明干预以保存白质束提供了更好的治疗可能性。损伤部位及周围白质的损失被认为是随后神经功能丧失的主要潜在原因。在这项研究中,我们使用了一系列技术,包括对有病变的轴突数量的估计、免疫组织化学和病变轴突分布的绘图,以更好地了解大鼠脊髓挫伤后白质中随时间推移的病理事件。最初有大量轴突迅速丧失,损伤后 1 周内没有检测到进一步的损失。CNPase 的免疫反应性表明,少突胶质细胞的变化是迅速的,延伸到离损伤部位几毫米远的地方,并且早于大部分轴突丧失,从而可以早期预测幸存的白质最终体积。在幼年大鼠中,白质束中的轴突髓鞘化似乎会持续一段时间,这对我们和以前的研究的解释有重要影响。髓磷脂碎片和轴突病变的数量随时间逐渐减少,但在损伤后 10 周仍可观察到,尤其是在离损伤部位更远的头侧和尾侧水平。这项研究提供了评估脊髓损伤的新方法,并表明需要早期干预才能在损伤后成功保留白质束。