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多发性硬化症灵长类动物模型中的脊髓病变谱。

The spectrum of spinal cord lesions in a primate model of multiple sclerosis.

机构信息

Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA/Institut du Cerveau et de la Moelle-ICM, Centre de NeuroImagerie de Recherche-CENIR, Sorbonne Universités, Paris, France.

Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

出版信息

Mult Scler. 2020 Mar;26(3):284-293. doi: 10.1177/1352458518822408. Epub 2019 Feb 7.

Abstract

BACKGROUND

Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a nonhuman primate model of multiple sclerosis (MS) that shares numerous clinical, radiological, and pathological features with MS. Among the clinical features are motor and sensory deficits that are highly suggestive of spinal cord (SC) damage.

OBJECTIVE

To characterize the extent and nature of SC damage in symptomatic marmosets with EAE using a combined magnetic resonance imaging (MRI) and histopathology approach.

MATERIALS AND METHODS

SC tissues from five animals were scanned using 7 T MRI to collect high-resolution ex vivo images. Lesions were segmented and classified based on shape, size, and distribution along the SC. Tissues were processed for histopathological characterization (myelin and microglia/macrophages). Statistical analysis, using linear mixed-effects models, evaluated the association between MRI and histopathology.

RESULTS

Marmosets with EAE displayed two types of SC lesions: focal and subpial lesions. Both lesion types were heterogeneous in size and configuration and corresponded to areas of marked demyelination with high density of inflammatory cells. Inside the lesions, the MRI signal was significantly correlated with myelin content ( < 0.001).

CONCLUSIONS

Our findings underscore the relevance of this nonhuman primate EAE model for better understanding mechanisms of MS lesion formation in the SC.

摘要

背景

食蟹猴实验性自身免疫性脑脊髓炎(EAE)是多发性硬化症(MS)的非人类灵长类动物模型,与 MS 具有许多临床、放射学和病理学特征。其中包括运动和感觉功能障碍,高度提示脊髓(SC)损伤。

目的

采用磁共振成像(MRI)和组织病理学相结合的方法,对有症状的 EAE 食蟹猴的 SC 损伤程度和性质进行特征描述。

材料和方法

使用 7T MRI 对 5 只动物的 SC 组织进行扫描,以收集高分辨率的离体图像。基于形状、大小和在 SC 上的分布对病变进行分割和分类。对组织进行组织病理学特征(髓鞘和小胶质细胞/巨噬细胞)处理。使用线性混合效应模型进行统计分析,以评估 MRI 和组织病理学之间的关联。

结果

患有 EAE 的食蟹猴表现出两种类型的 SC 病变:局灶性和软脊膜下病变。这两种病变类型在大小和形态上均存在异质性,与明显脱髓鞘区域以及高密度炎症细胞相对应。在病变内部,MRI 信号与髓鞘含量显著相关(<0.001)。

结论

我们的研究结果强调了这种非人类灵长类动物 EAE 模型对于更好地理解 MS 中 SC 病变形成机制的相关性。

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