An animal model of cortical and callosal pathology in multiple sclerosis.
An animal model of cortical and callosal pathology in multiple sclerosis.
复制标题
DOI：
10.1111/j.1750-3639.2010.00444.x
复制
发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Tiwari-Woodruff SK
中科院分区：
文献类型：
--
作者：
Mangiardi M;Crawford DK;Xia X;Du S;Simon-Freeman R;Voskuhl RR;Tiwari-Woodruff SK
多发性硬化症（MS）的病理学和放射学特征包括散布在中枢神经系统（CNS）白色物质中的多发性脱髓鞘病变。最近，大脑皮层已被证明是MS的影响，但由于缺乏反映这种人类皮质病理学的动物模型，导致皮质脱髓鞘的事件的阐明受到阻碍。在这份报告中，我们已经描述了存在的皮质灰质和胼胝体白色物质脱髓鞘病变的慢性实验性自身免疫性脑脊髓炎（EAE）小鼠模型MS。类似的MS患者的病理病变，EAE病变已被分类为I型-白皮质，II型-皮质内和III型-软膜下。所有这些病变都有不同程度的脱髓鞘、炎性细胞和反应性星形胶质细胞。与MS相似，EAE期间皮质层表现出脱髓鞘、小胶质细胞活化、突触蛋白改变和凋亡细胞。此外，EAE时胼胝体白色物质有许多炎性脱髓鞘病变和轴突变性。功能性电生理传导分析显示，在早期和晚期EAE的有髓和无髓胼胝体轴突的赤字。慢性EAE小鼠模型具有模拟MS的皮质和胼胝体病理学的特征，并且可以潜在地用于筛选药剂以预防疾病的这些特征。
The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.