Berger Cedric, Hiestand Peter, Kindler-Baumann Diana, Rudin Markus, Rausch Martin
Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
NMR Biomed. 2006 Feb;19(1):101-7. doi: 10.1002/nbm.1007.
In vivo tracking of macrophage migration is feasible by labeling cells with ultra-small particles of iron oxide (USPIO). It is demonstrated that it is possible to monitor distinct patterns of macrophage migration during the early states of inflammation in a rodent model of chronic relapsing experimental autoimmune encephalomyelitis (EAE). As previous MRI studies showed that EAE inflammation processes are clearly linked to macrophage infiltration in the brain, a longitudinal protocol for macrophage visualization was designed, where USPIOs were injected repeatedly during the acute phase of the disease, the remitting phase and the first relapse. In addition to USPIO-enhanced MRI, blood-brain barrier (BBB) damage, magnetization transfer ratios (MTRs) and neurological impairment were assessed as classical markers for central nervous system (CNS) inflammation and tissue damage. During the acute phase, animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue and some diffuse patterns of BBB disruption. While USPIO-accumulation completely disappeared after the acute phase, residual damage of the BBB remained detectable in some lesions during the remitting phase. During the first relapse, the accumulation of USPIO-loaded cells was less pronounced but still detectable. The time course of MTR, which is used as a marker for myelin loss, was linked to the infiltration of macrophages during the acute phase.
通过用超小氧化铁颗粒（USPIO）标记细胞，在体内追踪巨噬细胞迁移是可行的。研究表明，在慢性复发性实验性自身免疫性脑脊髓炎（EAE）啮齿动物模型的炎症早期，监测巨噬细胞迁移的不同模式是可能的。由于先前的MRI研究表明，EAE炎症过程与大脑中的巨噬细胞浸润明显相关，因此设计了一种巨噬细胞可视化的纵向方案，即在疾病的急性期、缓解期和首次复发期反复注射USPIO。除了USPIO增强的MRI外，还评估了血脑屏障（BBB）损伤、磁化传递率（MTR）和神经功能障碍，作为中枢神经系统（CNS）炎症和组织损伤的经典标志物。在急性期，动物表现出后肢严重麻痹，脑组织中巨噬细胞大量积聚，以及一些血脑屏障破坏的弥漫性模式。虽然急性期后USPIO的积聚完全消失，但在缓解期仍可在一些病变中检测到血脑屏障的残留损伤。在首次复发期间，负载USPIO的细胞积聚不太明显，但仍可检测到。用作髓鞘损失标志物的MTR的时间进程与急性期巨噬细胞的浸润有关。
