Early detection of the chemical changes occurring during the induction and prevention of autoimmune-mediated demyelination detected by FT-IR imaging
Early detection of the chemical changes occurring during the induction and prevention of autoimmune-mediated demyelination detected by FT-IR imaging
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DOI：
10.1016/j.neuroimage.2009.09.053
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发表时间：
2010-01-15
期刊：
影响因子：
5.7
通讯作者：
Bernard, Claude C. A.
中科院分区：
文献类型：
--
作者：
Heraud, Philip;Caine, Sally;Bernard, Claude C. A.
多发性硬化症 (MS) 是一种中枢神经系统 (CNS) 的炎症、脱髓鞘和神经退行性疾病。尽管在了解这种疾病的免疫遗传学方面取得了进展，但涉及病变形成的机制尚不清楚。为了获得对多发性硬化症神经病理学的新见解，我们创新性地将傅里叶变换红外 (FT-IR) 显微光谱学、生物信息学和同步加速器光源结合起来，分析实验性自身免疫性脑脊髓炎 (EAE)（一种多发性硬化症动物模型）的病程和预防过程中中枢神经系统的大分子变化。我们报告说，在 EAE 临床症状出现之前，检测到了传统组织学未观察到的细微化学和结构变化。此外，训练有素的人工神经网络（ANN）可以以优异的灵敏度和特异性区分周围组织的病理学和疾病进展的早期阶段。值得注意的是，我们表明，这种新颖的测量平台可以检测通过接种神经生长抑制剂 Nogo-A 部分预防 EAE 的动物病变病理生化成分的特征差异，这证明了自动筛选和评估新治疗药物的潜力。 (C) 2009 Elsevier Inc. 保留所有权利。
Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Despite progress in understanding immunogenetic aspects of this disease, the mechanisms involved in lesion formation are unknown. To gain new insights into the neuropathology of MS, we used an innovative integration of Fourier transform infrared (FT-IR) microspectroscopy, bioinformatics, and a synchrotron light source to analyze macromolecular changes in the CNS during the course and prevention of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We report that subtle chemical and structural changes not observed by conventional histology were detected before the onset of clinical signs of EAE. Moreover, trained artificial neural networks (ANNs) could discriminate, with excellent sensitivity and specificity, pathology from surrounding tissues and the early stage of the disease progression. Notably, we show that this novel measurement platform can detect characteristic differences in biochemical composition of lesion pathology in animals partially protected against EAE by vaccination with Nogo-A, an inhibitor of neural outgrowth, demonstrating the potential for automated screening and evaluation of new therapeutic agents. (C) 2009 Elsevier Inc. All rights reserved.