Rausch M, Hiestand P, Baumann D, Cannet C, Rudin M
Novartis Institute for Biomedical Research, Basel, Switzerland.
Magn Reson Med. 2003 Aug;50(2):309-14. doi: 10.1002/mrm.10541.
Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes.
实验性自身免疫性脑脊髓炎（EAE）是一种常用的动物模型，在多个方面模拟人类多发性硬化症（MS），可用于设计或验证治疗该疾病的新策略。在本研究中，采用了不同的MRI技术（基于超小氧化铁颗粒（USPIO）体内标记细胞的巨噬细胞追踪、血脑屏障（BBB）破坏和磁化传递成像（MTI））以及免疫组织化学染色，来研究豚鼠髓鞘免疫的Lewis大鼠的疾病负担。将所得的成像数据与行为读数进行比较。在急性期和首次复发期间对动物进行研究。在脑干或皮质的两个阶段均检测到活化的单核细胞。这些区域部分与BBB破坏区域重合。在USPIO积累区域观察到磁化传递率（MTR）显著变化，高达35%。这表明浸润的单核细胞是EAE中脱髓鞘的主要来源，但单核细胞浸润和BBB破坏是时间或空间上独立的炎症过程。
