Patel Vishal C, Jurgens Christopher W D, Krahe Thomas E, Povlishock John T
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
Exp Neurol. 2017 Mar;289:85-95. doi: 10.1016/j.expneurol.2016.12.012. Epub 2016 Dec 28.
The pathologic process in traumatic brain injury marked by delayed axonal loss, known as diffuse axonal injury (DAI), leads to partial deafferentation of neurons downstream of injured axons. This process is linked to persistent visual dysfunction following mild traumatic brain injury (mTBI), however, examination of deafferentation in humans is impossible with current technology. To investigate potential reorganization in the visual system following mTBI, we utilized the central fluid percussion injury (cFPI) mouse model of mTBI. We report that in the optic nerve of adult male C57BL/6J mice, axonal projections of retinal ganglion cells (RGCs) to their downstream thalamic target, dorsal lateral geniculate nucleus (dLGN), undergo DAI followed by scattered, widespread axon terminals loss within the dLGN at 4days post-injury. However, at 10days post-injury, significant reorganization of RGC axon terminals was found, suggestive of an adaptive neuroplastic response. While these changes persisted at 20days post-injury, the RGC axon terminal distribution did not recovery fully to sham-injury levels. Our studies also revealed that following DAI, the segregation of axon terminals from ipsilateral and contralateral eye projections remained consistent with normal adult mouse distribution. Lastly, our examination of the shell and core of dLGN suggested that different RGC subpopulations may vary in their susceptibility to injury or in their contribution to reorganization following injury. Collectively, these findings support the premise that subcortical axon terminal reorganization may contribute to recovery following mTBI, and that different neural phenotypes may vary in their contribution to this reorganization despite exposure to the same injury.
以延迟性轴突损伤为特征的创伤性脑损伤病理过程，即弥漫性轴突损伤（DAI），会导致受损轴突下游神经元的部分传入神经阻滞。这一过程与轻度创伤性脑损伤（mTBI）后持续的视觉功能障碍有关，然而，目前的技术无法对人类的传入神经阻滞进行检测。为了研究mTBI后视觉系统的潜在重组，我们利用了mTBI的中心流体冲击伤（cFPI）小鼠模型。我们报告，在成年雄性C57BL/6J小鼠的视神经中，视网膜神经节细胞（RGCs）向其下游丘脑靶标背外侧膝状核（dLGN）的轴突投射会发生DAI，随后在损伤后4天，dLGN内出现分散、广泛的轴突终末丢失。然而，在损伤后10天，发现RGC轴突终末有显著重组，提示存在适应性神经可塑性反应。虽然这些变化在损伤后20天持续存在，但RGC轴突终末分布并未完全恢复到假损伤水平。我们的研究还表明，DAI后，同侧和对侧眼投射的轴突终末分离仍与正常成年小鼠分布一致。最后，我们对dLGN的壳和核的检查表明，不同的RGC亚群在对损伤的易感性或损伤后对重组的贡献方面可能存在差异。总的来说，这些发现支持以下前提：皮层下轴突终末重组可能有助于mTBI后的恢复，并且尽管暴露于相同损伤，不同的神经表型对这种重组的贡献可能不同。
