Mild traumatic brain injury in the mouse induces axotomy primarily within the axon initial segment
Mild traumatic brain injury in the mouse induces axotomy primarily within the axon initial segment
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DOI：
10.1007/s00401-013-1119-4
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发表时间：
2013-07-01
影响因子：
12.7
通讯作者：
Povlishock, John T.
中科院分区：
文献类型：
--
作者：
Greer, John E.;Hanell, Anders;Povlishock, John T.
创伤性轴索损伤（TAI）是创伤性脑损伤（TBI）的一个固有组成部分，并与其大部分发病率相关。它也越来越多地被认为是轻度创伤性脑损伤（mTBI）的一种主要病理改变。在其发病机制方面，众多研究已经调查了郎飞结、结旁区和结间区对TAI的易感性。郎飞结因其独特的离子通道组成和浓度，被认为是损伤的主要部位，它引发了相关结旁和结间区域的一系列异常，导致局部轴索肿胀和脱离。然而，没有研究确定TAI对轴突起始段（AIS）的影响，而AIS是调节极性和兴奋性的关键部位。当前的研究试图确定新皮质内这些不同轴突区域对TAI的易感性，在新皮质中可以同时评估每个轴突区域。利用一种mTBI小鼠模型，在新皮质灰质内发现了轴突损伤的时空异质性。尽管在有髓新皮质轴突的所有区域都发现了轴突肿胀，但大部分TAI发生在AIS内，且在AIS本身没有明显结构破坏的情况下进展。发现AIS主要受累对于神经元极性和轴突切断过程的命运具有重要意义，同时也提出了治疗方面的启示，因为AIS中这种轴突损伤的潜在机制可能与所描述的结/结旁损伤的机制不同。
Traumatic axonal injury (TAI) is a consistent component of traumatic brain injury (TBI), and is associated with much of its morbidity. Increasingly, it has also been recognized as a major pathology of mild TBI (mTBI). In terms of its pathogenesis, numerous studies have investigated the susceptibility of the nodes of Ranvier, the paranode and internodal regions to TAI. The nodes of Ranvier, with their unique composition and concentration of ion channels, have been suggested as the primary site of injury, initiating a cascade of abnormalities in the related paranodal and internodal domains that lead to local axonal swellings and detachment. No investigation, however, has determined the effect of TAI upon the axon initial segment (AIS), a segment critical to regulating polarity and excitability. The current study sought to identify the susceptibility of these different axon domains to TAI within the neocortex, where each axonal domain could be simultaneously assessed. Utilizing a mouse model of mTBI, a temporal and spatial heterogeneity of axonal injury was found within the neocortical gray matter. Although axonal swellings were found in all domains along myelinated neocortical axons, the majority of TAI occurred within the AIS, which progressed without overt structural disruption of the AIS itself. The finding of primary AIS involvement has important implications regarding neuronal polarity and the fate of axotomized processes, while also raising therapeutic implications, as the mechanisms underlying such axonal injury in the AIS may be distinct from those described for nodal/paranodal injury.