Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury
Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury
复制标题
DOI：
10.1115/1.1324667
复制
发表时间：
2000-12-01
影响因子：
1.7
通讯作者：
Meaney, DF
中科院分区：
文献类型：
--
作者：
Bain, AC;Meaney, DF
在体内，通过将形态损伤和电生理损伤与体内轴突损伤模型中估计的组织应变进行比较，确定轴突损伤的组织水平机械阈值。轴突损伤是通过将成年雄性豚鼠的右视神经动态拉伸至七个眼位移水平之一（N水平=10；N总=70）而产生的。通过神经丝免疫组织化学染色（NF68、SM132）检测形态损伤。同时，通过拉伸前后记录的视觉诱发电位 (VEP) 的 N-35 峰潜伏期偏移的大小来确定功能损伤。一组配套的原位实验（N 级=5）用于确定所应用的眼位移和视神经拉伸幅度之间的经验关系。逻辑回归分析结合敏感性和特异性测量以及接受者操作特征（ROC）曲线用于预测轴突损伤的应变阈值。根据该分析，我们确定了三个基于拉格朗日应变的白质形态损伤阈值。自由阈值应变为 0.34，旨在最大限度地减少假阳性检测，保守阈值应变为 0.14，最大限度地减少假阴性率。平衡特异性和敏感性测量的最佳阈值应变标准是 0.21。对电生理损伤的类似比较产生了自由派、保守派、保守派、自由派和保守派。最佳应变阈值分别为 0.28、0.13 和 0.18。有了这些阈值数据，现在可以更准确地预测导致人类白质轴突损伤的情况。
In vivo, tissue-level, mechanical thresholds for axonal injury were determined by comparing morphological injury and electrophysiological impairment to estimated tissue strain in an in vivo model of axonal injury. Axonal injury was produced by-dynamically stretching the right optic nerve of an adult male guinea pig to one of seven levels of ocular displacement (N-level=10; N-total=70). Morphological injury was detected with neurofilament immunohistochemical staining (NF68, SM132). Simultaneously, functional injury was determined by the magnitude of the latency shift of the N-35 peak of the the visual evoked potentials (VEPs) recorded before and after stretch. A companion set of in situ experiments (N-level=5) was used to determine the empirical relationship between the applied ocular displacement and the magnitude of optic nerve stretch. Logistic regression analysis, combined with sensitivity and specificity measures and receiver operating characteristic (ROC) curves were used to predict strain thresholds for axonal injury. From this analysis, we determined three Lagrangian strain-based thresholds for morphological damage to white matter The liberal threshold, intended to minimize the detection of false positives, was a strain of 0.34, and the conservative threshold strain that minimized the false negative rate was 0.14. The optimal threshold strain criterion that balanced the specificity and sensitivity measures was 0.21. Similar comparisons for electrophysiological impairment produced liberal, conservative; and optimal strain thresholds of 0.28 0.13, and 0.18, respectively. With these threshold data, it is now possible to predict more accurately the conditions that cause axonal injury in human white matter.