Axonal Loss and Neurofilament Phosphorylation Changes Accompany Lesion Development and Clinical Progression in Multiple Sclerosis
Axonal Loss and Neurofilament Phosphorylation Changes Accompany Lesion Development and Clinical Progression in Multiple Sclerosis
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DOI：
10.1111/j.1750-3639.2010.00466.x
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发表时间：
2011-07-01
期刊：
影响因子：
6.4
通讯作者：
Stadelmann, Christine
中科院分区：
文献类型：
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作者：
Schirmer, Lucas;Antel, Jack P.;Stadelmann, Christine
神经轴突损伤和丧失越来越多地被认为是多发性硬化症（MS）病理学中的残疾决定特征。然而，很少有人知道的神经元和axons.Spinal脊髓组织的炎性脱髓鞘的长期后遗症31 MS患者进行了比较，3肌萎缩侧索硬化症（ALS）和10个对照组。根据KiM-1 P阳性巨噬细胞和小胶质细胞的密度以及髓鞘碱性蛋白（MBP）阳性吞噬细胞的存在对MS病变进行分期。在实质和脑膜中定量T细胞。免疫组化法检测神经轴突淀粉样前体蛋白（APP）和β-磷酸化神经丝（SMI 312、SMI 31、SMI 32）的变化。腹角神经元中SMI 32 IR的缺失与MS损伤发展和疾病进展相关。同样，白色物质（WM）病变中的轴突丢失与疾病持续时间相关。在WM病变中观察到轴突磷酸化神经丝（SMI 31）的选择性减少。在ALS中，神经元SMI 32 IR的损失甚至更明显，而轴突的相对减少类似于MS中发现的。慢性炎症性脱髓鞘背景下进行性神经轴突神经丝的改变可能反映了神经轴突代谢的变化，并导致慢性神经轴突功能障碍作为临床进展的假定底物。
Neuroaxonal damage and loss are increasingly recognized as disability determining features in multiple sclerosis (MS) pathology. However, little is known about the long-term sequelae of inflammatory demyelination on neurons and axons.Spinal cord tissue of 31 MS patients was compared to three amyotrophic lateral sclerosis (ALS) and 10 control subjects. MS lesions were staged according to the density of KiM-1P positive macrophages and microglia and the presence of myelin basic protein (MBP) positive phagocytes. T cells were quantified in the parenchyma and meninges. Neuroaxonal changes were studied by immunoreactivity (IR) for amyloid precursor protein (APP) and variably phosphorylated neurofilaments (SMI312, SMI31, SMI32).Little T cell infiltration was still evident in chronic inactive lesions. The loss of SMI32 IR in ventral horn neurons correlated with MS lesion development and disease progression. Similarly, axonal loss in white matter (WM) lesions correlated with disease duration. A selective reduction of axonal phosphorylated neurofilaments (SMI31) was observed in WM lesions. In ALS, the loss of neuronal SMI32 IR was even more pronounced, whereas the relative axonal reduction resembled that found in MS.Progressive neuroaxonal neurofilament alterations in the context of chronic inflammatory demyelination may reflect changes in neuroaxonal metabolism and result in chronic neuroaxonal dysfunction as a putative substrate of clinical progression.