Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, and axonal outgrowth in the axotomized neuronal population.
Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, and axonal outgrowth in the axotomized neuronal population.
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DOI：
10.1523/jneurosci.5103-10.2011
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发表时间：
2011-03-30
期刊：
影响因子：
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通讯作者：
Povlishock JT
中科院分区：
文献类型：
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作者：
Greer JE;McGinn MJ;Povlishock JT
创伤性轴索损伤 (TAI) 是创伤性脑损伤 (TBI) 的一个共同组成部分，并且与其大部分发病率相关。关于 TAI 的长期逆行神经元后果和/或 TAI 可能导致顺行轴突重组和修复的潜力知之甚少。为了研究 TIA 引发的顺行和逆行反应的全部内容，对 Thy1-YFP-H 小鼠进行轻度中枢液体冲击损伤，并在损伤后 15 分钟至 28 天之间的不同时间处死。基于内源性神经元荧光的共聚焦评估，发现这种损伤会导致 YFP+ 轴突内新皮质第五层的弥漫性 TAI。当这些荧光方法与各种定量和免疫组织化学方法相结合时，我们发现这种 TAI 在评估的 28 天期间不会导致神经元死亡。相反，它引起了神经元萎缩。在这些相同的轴突神经元群体中，TAI 还被发现能诱导转录因子 c-Jun 和 ATF-3（已知的轴突再生调节因子）的早期持续激活。平行超微结构研究证实，在没有神经元死亡的情况下，这些反应性变化与萎缩一致。与神经元细胞体中发生的这些事件同时发生，其下游轴突节段早在损伤后 1 天就显示出与反应性出芽一致的形态变化，并伴随着随着时间的推移显着的轴突伸长。总的来说，这些与 TAI 相关的事件与持续的神经元恢复、再生遗传程序的激活以及随后暗示某种形式的再生反应的轴突重组一致。
Traumatic axonal injury (TAI) is a consistent component of traumatic brain injury (TBI), and is associated with much of its morbidity. Little is known regarding the long-term retrograde neuronal consequences of TAI and/or the potential that TAI could lead to anterograde axonal reorganization and repair. To investigate the repertoire of anterograde and retrograde responses triggered by TIA, Thy1-YFP-H mice were subjected to mild central fluid percussion injury and sacrificed at various times between 15 minutes and 28 days post-injury. Based upon confocal assessment of the endogenous neuronal fluorescence, such injury was found to result in diffuse TAI throughout Layer V of the neocortex within YFP+ axons. When these fluorescent approaches were coupled with various quantitative and immunohistochemical approaches we found that this TAI did not result in neuronal death over the 28 day period assessed. Rather, it elicited neuronal atrophy. Within these same axotomized neuronal populations TAI was also found to induce an early and sustained activation of the transcription factors, c-Jun and ATF-3, known regulators of axon regeneration. Parallel ultrastructural studies confirmed these reactive changes consistent with atrophy, in the absence of neuronal death. Concurrent with those events ongoing in the neuronal cell bodies, their downstream axonal segments revealed, as early as 1 day post-injury, morphological changes consistent with reactive sprouting that was accompanied by significant axonal elongation over time. Collectively, these TAI-linked events are consistent with sustained neuronal recovery, an activation of a regenerative genetic program and subsequent axonal reorganization suggestive of some form of regenerative response.