Maxwell William L, Bartlett Emma, Morgan Hanna
Department of Anatomy, University of Glasgow, Glasgow, United Kingdom.
J Neurotrauma. 2015 Jun 1;32(11):780-90. doi: 10.1089/neu.2014.3369. Epub 2015 Mar 12.
Patients with chronic traumatic encephalopathy (CTE) show loss of central white matter, central gray matter, and cortical gray matter with increasing post-traumatic survival. The majority of experimental studies using animals have, however, discussed only the ultrastructural pathophysiology of injured central white matter leading to secondary axotomy and the formation of axonal terminal bulbs. Using the stretch-injured optic nerve model in adult guinea pigs, the present study provides novel quantitative data concerning Wallerian degeneration of disconnected axonal fragments following secondary axotomy out to 12 weeks after injury to an optic nerve. The time course of Wallerian degeneration at the level of an individual nerve fiber is comparable to that reported in earlier studies over 48 h to two weeks after secondary axotomy. But only a relatively small proportion of nerve fibers within the optic tract degenerate via Wallerian degeneration during the first two weeks. Rather, examples of each of the three stages of Wallerian degeneration-acute axonal degeneration, latency of the distal axonal segment, and granular fragmentation-occur within the optic tract across the entire experimental survival of 12 weeks used in the present study. This data suggests that some nerve fibers initiate Wallerian degeneration days and weeks after the initial time of mechanical injury to an optic nerve. The number of intact nerve fibers continues to fall over at least three months after injury in the stretch-injury model of traumatic axonal injury. It is suggested that these novel findings relate to the mechanism(s) whereby central white matter volume decreases over months and years in CTE patients.
慢性创伤性脑病（CTE）患者随着创伤后存活时间的增加，会出现中枢白质、中枢灰质和皮质灰质的丢失。然而，大多数使用动物的实验研究仅讨论了受伤中枢白质导致继发性轴突切断和轴突终球形成的超微结构病理生理学。本研究利用成年豚鼠的拉伸损伤视神经模型，提供了关于视神经损伤后12周内继发性轴突切断后断开的轴突片段沃勒变性的新定量数据。单个神经纤维水平的沃勒变性时间进程与早期研究报道的继发性轴突切断后48小时至两周的时间进程相当。但在最初两周内，视束内只有相对较小比例的神经纤维通过沃勒变性发生退化。相反，在本研究使用的12周整个实验存活期内，视束内出现了沃勒变性的三个阶段——急性轴突变性、远端轴突段潜伏期和颗粒状碎裂——的实例。这些数据表明，一些神经纤维在视神经受到机械损伤后的数天和数周后开始沃勒变性。在创伤性轴突损伤的拉伸损伤模型中，损伤后至少三个月内完整神经纤维的数量持续下降。有人认为，这些新发现与CTE患者中枢白质体积在数月和数年内减少的机制有关。
