Pomeroy Ian M, Matthews Paul M, Frank Joseph A, Jordan Elaine K, Esiri Margaret M
Department of Neuropathology, Radcliffe Infirmary, Oxford, UK.
Brain. 2005 Nov;128(Pt 11):2713-21. doi: 10.1093/brain/awh626. Epub 2005 Sep 8.
The use of immunohistochemical methods has led to a new understanding of the prevalence and significance of cortical lesions in multiple sclerosis but these lesions have not yet been formally described in an animal model. In this study we have set out to use immunohistochemical techniques to identify and describe cortical lesions in marmosets with experimental autoimmune encephalomyelitis (EAE). Using antibodies to proteolipid protein (PLP), we found a total of 70 cortical lesions in 11 tissue blocks from 6 animals. These lesions were subdivided into leucocortical (40), intracortical (12) and subpial lesions (18). We quantified the density of inflammatory cells within lesions using a double labelling protocol which employed anti-PLP in addition to antibodies against markers of B-lymphocytes (CD20), T-lymphocytes (CD3), macrophages (MAC387) and MHC-II expressing cells (CR3/43). This analysis revealed that the large subpial lesions accounted for the majority of demyelinated cortex (88%) despite possessing the lowest density of inflammatory cells. This study has shown that lesions in this model share many of the major features of cortical lesions in multiple sclerosis both in terms of morphology and inflammatory cell content. We believe that this tool can be exploited in future studies to investigate the aetiology, development and clinical significance of cortical lesions in demyelinating disease.
免疫组织化学方法的应用使人们对多发性硬化症中皮质病变的患病率和重要性有了新的认识,但这些病变尚未在动物模型中得到正式描述。在本研究中,我们着手使用免疫组织化学技术来识别和描述患有实验性自身免疫性脑脊髓炎(EAE)的狨猴的皮质病变。使用针对蛋白脂蛋白(PLP)的抗体,我们在来自6只动物的11个组织块中总共发现了70个皮质病变。这些病变被细分为白质皮质病变(40个)、皮质内病变(12个)和软脑膜下病变(18个)。我们使用双重标记方案对病变内炎症细胞的密度进行了量化,该方案除了使用抗B淋巴细胞(CD20)、T淋巴细胞(CD3)、巨噬细胞(MAC387)和表达MHC-II的细胞(CR3/43)的抗体外,还使用了抗PLP抗体。该分析表明,尽管软脑膜下大病变的炎症细胞密度最低,但它们占脱髓鞘皮质的大部分(88%)。这项研究表明,该模型中的病变在形态和炎症细胞含量方面与多发性硬化症中的皮质病变具有许多主要特征。我们相信,这个工具可在未来的研究中用于调查脱髓鞘疾病中皮质病变的病因、发展和临床意义。