Experimental and Regenerative Neurosciences, The University of Western Australia, Crawley, WA, Australia.
J Neurotrauma. 2011 Jun;28(6):1077-88. doi: 10.1089/neu.2010.1665. Epub 2011 May 5.
Secondary degeneration is a serious consequence of traumatic injury to the central nervous system (CNS) and involves the progressive loss of neurons and function. However, while disruption to myelin has been observed in spared axons, the ultrastructural abnormalities that occur in myelin and axons spatially separated from the primary injury and susceptible exclusively to secondary degeneration are unknown. We used a model of secondary degeneration in which the dorsal aspect of rat optic nerve (ON) was transected leaving the central/ventral ON undamaged, but vulnerable to secondary degeneration. Transmission electron microscopy of the central/ventral ON at 1 and 3 months was used to quantify secondary changes in axon diameter, myelin sheath thickness and morphology, compared to normal animals. Three months after partial ON transection, cross-sectional nerve area at the injury site was increased (p ≤ 0.05), and changes in axons and myelin sheaths were detected in the central/ventral ON. Although myelin sheath thickness remained normal at both time points, average axon diameter significantly increased at 3 months. The density of the total axon population was decreased by 1 month, reflecting loss of retinal ganglion cells as previously published, with a decrease in the density of normally-myelinated axons, but an increase in unmyelinated axon density (p ≤ 0.05). Myelin basic protein immunoreactivity and fluoromyelin staining were also significantly reduced. Within four subpopulations of abnormally-myelinated axons, there was: no change in lightly-myelinated axons; an increase in axons with excessive myelination (at 1 month); and an increase in the density of axons with partial and fully-decompacted myelin (at 3 months, p ≤ 0.05). Chronic axon swelling and myelin sheath compaction defects are features of secondary degeneration, and may contribute to the reported loss of ON function following partial transection.
继发性退化是中枢神经系统（CNS）创伤后的严重后果，涉及神经元和功能的逐渐丧失。然而，虽然在 spared axons 中观察到了髓鞘的破坏，但在远离原发性损伤且仅易发生继发性退化的髓鞘和轴突的超微结构异常尚不清楚。我们使用了一种继发性退化模型，其中大鼠视神经（ON）的背侧被横断，而中央/腹侧 ON 未受损，但易受继发性退化影响。使用透射电子显微镜对中央/腹侧 ON 在 1 个月和 3 个月时进行观察，以定量分析与正常动物相比，轴突直径、髓鞘厚度和形态的继发性变化。部分 ON 横断后 3 个月，损伤部位的神经横截面积增加（p≤0.05），并在中央/腹侧 ON 中检测到轴突和髓鞘的变化。尽管在两个时间点髓鞘厚度均保持正常，但 3 个月时平均轴突直径显著增加。1 个月时总轴突群体密度降低，反映了先前发表的视网膜神经节细胞的丢失，正常髓鞘化轴突的密度降低，但未髓鞘化轴突的密度增加（p≤0.05）。髓鞘碱性蛋白免疫反应性和荧光髓鞘染色也显著降低。在异常髓鞘化轴突的四个亚群中：轻度髓鞘化轴突无变化；过度髓鞘化轴突增加（1 个月）；部分和完全去压缩髓鞘的轴突密度增加（3 个月，p≤0.05）。慢性轴突肿胀和髓鞘压缩缺陷是继发性退化的特征，可能导致部分横断后报道的 ON 功能丧失。
