Cardenas Agustin M, Sarlls Joelle E, Kwan Justin Y, Bageac Devin, Gala Zachary S, Danielian Laura E, Ray-Chaudhury Abhik, Wang Hao-Wei, Miller Karla L, Foxley Sean, Jbabdi Saad, Welsh Robert C, Floeter Mary Kay
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Department of Neurology, University of Maryland, Baltimore, MD, United States.
Neuroimage Clin. 2017 Apr 30;15:200-208. doi: 10.1016/j.nicl.2017.04.024. eCollection 2017.
The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients.
Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters.
The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with mutations, and increased reactive astrocytes throughout the callosum.
Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role.
本研究的目的是更好地理解肌萎缩侧索硬化症（ALS）患者白质扩散变化背后的组织微观结构变化。
在7T MRI扫描仪上，使用稳态自由进动序列对4例ALS患者和2例无神经疾病受试者的死后大脑进行扩散张量成像。在福尔马林固定的半球中，测量胼胝体膝部、体部和压部的分数各向异性（FA）。胼胝体体部和膝部的FA表示为与压部FA的比值，压部是ALS中未受影响的区域。成像后，对胼胝体相同节段的组织切片进行不同组织成分标记物的染色。由不知情的评分者对编码图像区域的病理变化进行评分。
与对照组相比，ALS患者的FA体部/FA压部比值降低。仅在ALS患者胼胝体体部观察到髓鞘苍白的斑片状区域以及对小胶质细胞-巨噬细胞标记物CD68进行免疫染色的细胞。不知情评分显示，ALS患者胼胝体体部CD68+小胶质细胞增多，尤其是那些有突变的患者，并且整个胼胝体中反应性星形胶质细胞增多。
ALS患者胼胝体FA降低是由组织微观结构的复杂变化所致。FA降低的胼胝体节段除了有髓鞘轴突丢失和星形胶质细胞增生外，还有大量小胶质细胞-巨噬细胞。小胶质细胞炎症导致ALS患者FA降低，可能促成促炎状态，但需要进一步研究以确定它们的作用。
