Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging

Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging
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DOI:
10.1002/jmri.20057
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发表时间:
2004-07-01
影响因子:
4.4
通讯作者:
Rudin, M
Rudin, M
中科院分区:
医学2区
文献类型:
--
作者:
Rausch, M;Hiestand, P;Rudin, M

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用途:为了研究FTY 720作为一种新的代理,以减少炎症活动的多发性硬化症(MS)的动物模型中的体内macrophage tracking.Material and Methods:FTY 720被用于治疗大鼠慢性复发性实验性自身免疫性脑脊髓炎(EAE)的模型中,口服剂量为0.3毫克/公斤/天。使用基于超小超顺磁性氧化铁(USPIO)纳米颗粒标记的巨噬细胞的体内跟踪的磁共振成像(MRI)、免疫组织学染色(IHC)和神经学读数来研究治疗和未治疗动物的疾病负担。而未处理的动物显示出后爪的严重麻痹,脑组织中巨噬细胞的大量积累,和血脑屏障(131313)破坏的区域,FTY 720治疗的动物没有显示出炎症活动或神经损伤的迹象。这些意见都作出了急性期和第一recursion.Conclusion:通过MRI跟踪巨噬细胞FTY 720在EAE模型中的免疫调节功效提供了直接的证据,并与神经症状和组织学相关。
Purpose: To examine the efficacy of FTY720 as a new agent to reduce inflammatory activity in an animal model of multiple sclerosis (MS) by in vivo macrophage tracking.Material and Methods: FTY720 was used for treatment of rats in a model of chronic relapsing experimental autoimmune encephalomyelitis (EAE) at an oral dose of 0.3 mg/kg/day. Magnetic resonance imaging (MRI) based on in vivo tracking of macrophages labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, immunohistological staining (IHC), and neurological readouts was used to study the burden of disease in treated and untreated animals.Results: While untreated animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue, and areas of blood-brain barrier (131313) disruption, FTY720-treated animals displayed no signs of inflammatory activity or neurological impairment. These observations were made for both acute phase and first relapse.Conclusion: Tracking of macrophages by MRI provides direct evidence of the immunomodulatory efficacy of FTY720 in the EAE model and correlates well with neurological symptoms and histology.