Nashmi R, Fehlings M G
Division of Neurosurgery and the University Health Network, The Toronto Western Hospital Research Institute, Institute of Medical Science, University of Toronto, M5T 2S8, Toronto, Canada.
Neuroscience. 2001;104(1):235-51. doi: 10.1016/s0306-4522(01)00009-4.
The spinal cord is rarely transected after spinal cord injury. Dysfunction of surviving axons, which traverse the site of spinal cord injury, appears to contribute to post-traumatic neurological deficits, although the underlying mechanisms remain unclear. The subpial rim frequently contains thinly myelinated axons which appear to conduct signals abnormally, although it is uncertain whether this truly reflects maladaptive alterations in conduction properties of injured axons during the chronic phase of spinal cord injury or whether this is merely the result of the selective survival of a subpopulation of axons. In the present study, we examined the changes in axonal conduction properties after chronic clip compression injury of the rat thoracic spinal cord, using the sucrose gap technique and quantitatively examined changes in the morphological and ultrastructural features of injured axonal fibers in order to clarify these issues. Chronically injured dorsal columns had a markedly reduced compound action potential amplitude (8.3% of control) and exhibited significantly reduced excitability. Other dysfunctional conduction properties of injured axons included a slower population conduction velocity, a longer refractory period and a greater degree of high-frequency conduction block at 200 Hz. Light microscopic and ultrastructural analysis showed numerous axons with abnormally thin myelin sheaths as well as unmyelinated axons in the injured spinal cord. The ventral column showed a reduced median axonal diameter and the lateral and dorsal columns showed increased median diameters, with evidence of abnormally large swollen axons. Plots of axonal diameter versus myelination ratio showed that post-injury, dorsal column axons of all diameters had thinner myelin sheaths. Noninjured dorsal column axons had a median myelination ratio (1.56) which was within the optimal range (1.43-1.67) for axonal conduction, whereas injured dorsal column axons had a median myelination ratio (1.33) below the optimal value. These data suggest that maladaptive alterations occur postinjury to myelin sheath thickness which reduce the efficiency of axonal signal transmission.In conclusion, chronically injured dorsal column axons show physiological evidence of dysfunction and morphological changes in axonal diameter and reduced myelination ratio. These maladaptive alterations to injured axons, including decrease in myelin thickness and the appearance of axonal swellings, contribute to the decreased excitability of chronically injured axons. These results further clarify the mechanisms underlying neurological dysfunction after chronic neurotrauma and have significant implications regarding approaches to augment neural repair and regeneration.
脊髓损伤后脊髓很少发生横断。穿过脊髓损伤部位的存活轴突功能障碍似乎导致了创伤后神经功能缺损，尽管其潜在机制尚不清楚。软膜边缘通常含有薄髓鞘轴突，这些轴突似乎传导信号异常，尽管尚不确定这是否真的反映了脊髓损伤慢性期受损轴突传导特性的适应性改变，或者这仅仅是轴突亚群选择性存活的结果。在本研究中，我们使用蔗糖间隙技术研究了大鼠胸段脊髓慢性夹闭压迫损伤后轴突传导特性的变化，并定量检查了受损轴突纤维的形态和超微结构特征的变化，以阐明这些问题。慢性损伤的后索复合动作电位幅度明显降低（为对照的8.3%），并且兴奋性显著降低。受损轴突的其他功能障碍性传导特性包括群体传导速度减慢、不应期延长以及在200Hz时高频传导阻滞程度更大。光镜和超微结构分析显示，受损脊髓中有许多髓鞘异常薄的轴突以及无髓鞘轴突。腹侧柱的轴突中位直径减小，而外侧和背侧柱的中位直径增大，有异常大的肿胀轴突的证据。轴突直径与髓鞘化比率的关系图显示，损伤后，所有直径的背侧柱轴突髓鞘都更薄。未受损的背侧柱轴突的中位髓鞘化比率（1.56）在轴突传导的最佳范围内（1.43 - 1.67），而受损的背侧柱轴突的中位髓鞘化比率（1.33）低于最佳值。这些数据表明，损伤后髓鞘厚度发生适应性改变，降低了轴突信号传递的效率。总之，慢性损伤的背侧柱轴突显示出功能障碍的生理学证据以及轴突直径和髓鞘化比率降低的形态学变化。这些对受损轴突的适应性改变，包括髓鞘厚度的减少和轴突肿胀的出现，导致慢性损伤轴突的兴奋性降低。这些结果进一步阐明了慢性神经创伤后神经功能障碍的潜在机制，并对增强神经修复和再生的方法具有重要意义。
