Ha Grace K, Parikh Shivani, Huang Zhi, Petitto John M
Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
J Neuroimmunol. 2008 Aug 13;199(1-2):18-23. doi: 10.1016/j.jneuroim.2008.04.027. Epub 2008 Jun 6.
The temporal relationship between severity of peripheral axonal injury and T lymphocyte trafficking to the neuronal cell bodies of origin in the brain has been unclear. We sought to test the hypothesis that greater neuronal death induced by disparate forms of peripheral nerve injury would result in differential patterns of T cell infiltration and duration at the cell bodies of origin in the brain and that these measures would correlate with the magnitude of neuronal death over time and cumulative neuronal loss. To test this hypothesis, we compared the time course of CD3(+) T cell infiltration and neuronal death (assessed by CD11b(+) perineuronal microglial phagocytic clusters) following axonal crush versus axonal resection injuries, two extreme variations of facial nerve axotomy that result in mild versus severe neuronal loss, respectively, in the facial motor nucleus. We also quantified the number of facial motor neurons present at 49 days post-injury to determine whether differences in the levels of neuronal death between nerve crush and resection correlated with differences in cumulative neuronal loss. Between 1 and 7 days post-injury when levels of neuronal death were minimal, we found that the rate of accumulation and magnitude of the T cell response was similar following nerve crush and resection. Differences in the T cell response were apparent by 14 days post-injury when the level of neuronal death following resection was substantially greater than that seen in crush injury. For nerve resection, the peak of neuronal death at 14 days post-resection was followed by a maximal T cell response one week later at 21 days. Differences in the level of neuronal death between the two injuries across the time course tested reflected differences in cumulative neuronal loss at 49 days post-injury. Altogether, these data suggest that the trafficking of T cells to the injured FMN is dependent upon the severity of peripheral nerve injury and associated neuronal death.
外周轴突损伤的严重程度与T淋巴细胞向脑内起源神经元细胞体的迁移之间的时间关系尚不清楚。我们试图验证以下假设：不同形式的外周神经损伤所诱导的更严重的神经元死亡，将导致T细胞浸润模式及在脑内起源细胞体处的持续时间存在差异，并且这些指标将随时间与神经元死亡的程度以及累积神经元损失相关联。为验证这一假设，我们比较了轴突挤压伤与轴突离断伤后CD3(+) T细胞浸润和神经元死亡（通过CD11b(+)神经元周围小胶质细胞吞噬簇评估）的时间进程，这两种面神经切断术的极端变体分别导致面神经运动核中轻度与重度神经元损失。我们还对损伤后49天存在的面神经运动神经元数量进行了量化，以确定神经挤压伤和离断伤之间神经元死亡水平的差异是否与累积神经元损失的差异相关。在损伤后1至7天，当神经元死亡水平最低时，我们发现神经挤压伤和离断伤后T细胞反应的积累速率和幅度相似。损伤后14天，当离断伤后的神经元死亡水平明显高于挤压伤时，T细胞反应的差异变得明显。对于神经离断伤，离断后14天神经元死亡达到峰值，随后在1周后的21天出现最大T细胞反应。在所测试的时间进程中，两种损伤之间神经元死亡水平的差异反映了损伤后49天累积神经元损失的差异。总之，这些数据表明T细胞向受损面神经运动核的迁移取决于外周神经损伤的严重程度及相关的神经元死亡。
