Meeson A P, Piddlesden S, Morgan B P, Reynolds R
Department of Anatomy, Charing Cross and Westminister Medical School, London, United Kingdom.
Exp Neurol. 1994 Oct;129(2):299-310. doi: 10.1006/exnr.1994.1172.
Experimental allergic encephalomyelitis (EAE) has long been studied as an animal model of the human demyelinating disease Multiple Sclerosis. However, EAE induced in the Lewis rat by injection of myelin basic protein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammatory condition of the central nervous system (CNS) with little or no demyelination. In EAE models in which demyelination does result, it is either not very widespread or is unpredictable in its degree and location. In this study we have produced antibody-augmented demyelinating EAE (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts, followed by injection 4 days later of a monoclonal antibody against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory cell infiltrates and demyelination throughout the CNS using histochemistry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the folia. Perivascular, periventricular, and subpial inflammation was widespread throughout the pons/medulla and at all levels of the spinal cord. Very little inflammation was apparent in the forebrain. MBP immunofluorescence demonstrated extensive areas of periventricular demyelination in the forebrain around the third ventricle. Both periventricular and perivascular lesions were commonly observed in the cerebellum and pons/medulla. The extent of demyelination in the spinal cord increased caudally with large confluent areas of subpial demyelination seen throughout the lumbar cord. The extensive and reproducible distribution of inflammatory demyelinating lesions in ADEAE provide the possibility to select areas of the CNS for more detailed analysis of the cellular changes that accompany demyelination and remyelination.
实验性自身免疫性脑脊髓炎（EAE）长期以来一直被作为人类脱髓鞘疾病多发性硬化症的动物模型进行研究。然而，通过注射髓鞘碱性蛋白（MBP）或MBP特异性T淋巴细胞在Lewis大鼠中诱导的EAE，主要是中枢神经系统（CNS）的一种炎症状态，几乎没有脱髓鞘现象。在确实会导致脱髓鞘的EAE模型中，脱髓鞘要么不太广泛，要么在程度和位置上不可预测。在本研究中，我们通过注射活化的MBP特异性T淋巴母细胞，然后在4天后注射一种针对髓鞘/少突胶质细胞糖蛋白（一种髓鞘外在蛋白）的单克隆抗体，在Lewis大鼠中产生了抗体增强型脱髓鞘性EAE（ADEAE）。我们使用组织化学、免疫荧光和图像分析记录了整个CNS中炎症细胞浸润和脱髓鞘的程度及位置。在小脑深部白质和小叶中可见血管周围炎症浸润。血管周围、脑室周围和软膜下炎症在脑桥/延髓以及脊髓的各个水平广泛存在。前脑几乎没有明显炎症。MBP免疫荧光显示第三脑室周围前脑有广泛的脑室周围脱髓鞘区域。脑室周围和血管周围病变在小脑和脑桥/延髓中都很常见。脊髓中的脱髓鞘程度在尾部增加，在整个腰髓可见大片融合的软膜下脱髓鞘区域。ADEAE中炎症性脱髓鞘病变广泛且可重复的分布为选择CNS区域以更详细分析伴随脱髓鞘和再髓鞘化的细胞变化提供了可能性。
