Rostrocaudal analysis of corpus callosum demyelination and axon damage across disease stages refines diffusion tensor imaging correlations with pathological features.
Rostrocaudal analysis of corpus callosum demyelination and axon damage across disease stages refines diffusion tensor imaging correlations with pathological features.
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DOI：
10.1097/nen.0b013e3181e3de90
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发表时间：
2010-07
影响因子：
3.2
通讯作者：
Armstrong RC
中科院分区：
文献类型：
--
作者：
Xie M;Tobin JE;Budde MD;Chen CI;Trinkaus K;Cross AH;McDaniel DP;Song SK;Armstrong RC
对轴突损伤进展的非侵入性评估对于评估多发性硬化症 (MS) 患者的疾病进展和制定神经保护干预措施非常重要。我们使用 C57BL/6 和 Thy1-YFP-16 小鼠胼胝体铜宗脱髓鞘模型，检查了在整个脱髓鞘急性（4 周）和慢性（12 周）阶段以及恢复 6 周后与扩散张量成像 (DTI) 衍生的轴向 (λ||) 和径向 (λ⊥) 扩散率值相关的细胞反应。胼胝体病理改变的头尾进展使病理特征与 DTI 测量在空间和时间上确定相关性。在急性脱髓鞘过程中，小胶质细胞/巨噬细胞激活最广泛，轴突表现出肿胀、神经丝去磷酸化和直径减小。轴向扩散率值在急性期下降，但与慢性脱髓鞘期间的轴突萎缩无关。相反，径向扩散率随着脱髓鞘的进展而增加，但与髓鞘缺失或星形胶质细胞增生无关。与其他具有进行性神经变性和轴突丧失的动物模型不同，即使经过一段时间的慢性脱髓鞘，急性轴突损伤也不会发展为轴突的不连续或丧失。可逆性轴突病理、脱髓鞘、小胶质细胞/巨噬细胞激活和星形胶质细胞增生与区域轴向和径向扩散率测量的相关性将促进 DTI 在 MS 患者中的临床应用。
Non-invasive assessment of the progression of axon damage is important for evaluating disease progression and developing neuroprotective interventions in multiple sclerosis (MS) patients. We examined the cellular responses correlated with diffusion tensor imaging (DTI)-derived axial (λ||) and radial (λ⊥) diffusivity values throughout acute (4 weeks) and chronic (12 weeks) stages of demyelination and after 6 weeks of recovery using the cuprizone demyelination of the corpus callosum model in C57BL/6 and Thy1-YFP-16 mice. The rostro-caudal progression of pathologic alterations in the corpus callosum enabled spatially and temporally defined correlations of pathological features with DTI measurements. During acute demyelination, microglial/macrophage activation was most extensive and axons exhibited swellings, neurofilament dephosphorylation, and reduced diameters. Axial diffusivity values decreased in the acute phase but did not correlate with axonal atrophy during chronic demyelination. In contrast, radial diffusivity increased with the progression of demyelination but did not correlate with myelin loss or astrogliosis. Unlike other animals models with progressive neurodegeneration and axon loss, the acute axon damage did not progress to discontinuity or loss of axons even after a period of chronic demyelination. Correlations of reversible axon pathology, demyelination, microglia/macrophage activation, and astrogliosis with regional axial and radial diffusivity measurements will facilitate the clinical application of DTI in MS patients.