Magnetic resonance imaging characterization of different experimental autoimmune encephalomyelitis models and the therapeutic effect of glatiramer acetate
Magnetic resonance imaging characterization of different experimental autoimmune encephalomyelitis models and the therapeutic effect of glatiramer acetate
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DOI：
10.1016/j.expneurol.2012.11.004
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发表时间：
2013-02-01
影响因子：
5.3
通讯作者：
Arnon, Ruth
中科院分区：
文献类型：
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作者：
Aharoni, Rina;Sasson, Efrat;Arnon, Ruth
炎症、变性和灰质异常在多发性硬化（MS）及其实验性自身免疫性脑脊髓炎（EAE）动物模型中的作用存在争议。我们分析了两种EAE模型的病理表现，慢性少突胶质细胞糖蛋白（MOG）诱导与复发缓解蛋白脂质蛋白（PLP）诱导，沿着疾病进展，使用先进的磁共振成像（MRI）参数。本研究的重点是通过直方图分析对整个大脑进行总体评估，以及通过基于体素的分析（VXI）使用定量T2、磁化传递比（MTR）和扩散张量成像（DTI）检测特定受影响区域。来自两种模型的EAE致伤小鼠的大脑显示多个白色和灰质区域，对于所有MRI参数，与未处理小鼠相比具有显著变化。支气管肿胀更具有PLP诱导模型的特征。主要在MOG诱导的EAE中观察到MTR值降低和表观扩散系数（ADC）增加，表明慢性疾病中涉及大分子损失和结构性CNS损伤。MS药物醋酸格拉替雷（GA），无论是作为预防或治疗性治疗，影响所有的MRI病理表现，导致减少的12值和心室体积，MTR升高和ADC降低，与未经处理的EAE-造成的小鼠相比。与此雅阁的是，免疫组化分析表明GA处理后组织学损伤较少，增殖的少突胶质祖细胞数量较多。在全脑水平和特定区域中由MRI参数反映的更高的脑组织完整性支持GA治疗的原位抗炎和神经保护结果。(C)2012 Elsevier Inc. All rights reserved.
The roles of inflammation and degeneration as well as of gray matter abnormalities in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are controversial. We analyzed the pathological manifestations in two EAE models, the chronic oligodendrocyte glycoprotein (MOG)-induced versus the relapsing-remitting proteolipid protein (PLP)-induced, along the disease progression, using advanced magnetic resonance imaging (MRI) parameters. The emphasis of this study was the overall assessment of the whole brain by histogram analysis, as well as the detection of specific affected regions by voxel based analysis (VBA) using quantitative T2, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Brains of EAE-inflicted mice from both models revealed multiple white and gray matter areas with significant changes from naive mice for all MRI parameters. Ventricle swelling was more characteristic to the PLP-induced model. Decreased MTR values and increased apparent diffusion coefficient (ADC) were observed mainly in MOG-induced EAE, indicative of macromolecular loss and structural CNS damage involvement in the chronic disease. The MS drug glatiramer acetate (GA), applied either as prevention or therapeutic treatment, affected all the MRI pathological manifestations, resulting in reduced 12 values and ventricle volume, elevated MTR and decreased ADC, in comparison to untreated EAE-inflicted mice. In accord, immunohistochemical analysis indicated less histological damage and higher amount of proliferating oligodendrocyte progenitor cells after GA treatment. The higher brain tissue integrity reflected by the MRI parameters on the level of the whole brain and in specific regions supports the in situ anti-inflammatory and neuroprotective consequences of GA treatment. (C) 2012 Elsevier Inc. All rights reserved.