Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions
Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions
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DOI：
10.1002/ana.1123
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发表时间：
2001-09-01
影响因子：
11.2
通讯作者：
Trapp, BD
中科院分区：
文献类型：
--
作者：
Peterson, JW;Bö, L;Trapp, BD
多发性硬化症（MS）是一种中枢神经系统炎性脱髓鞘疾病，可导致运动、感觉和认知缺陷。本研究的特点是脱髓鞘病变的大脑皮层的MS患者。在50例MS患者的110个组织块中确定了112个皮质病变。确定了三种类型的皮质脱髓鞘：I型病变与皮质下白色病变相邻; II型病变较小，局限于皮质，通常为血管周围; III型病变从软脑膜表面延伸至皮质层3或4。炎症和神经元病理学进行了研究，分别从8名和7名患者的组织。与白色病变相比，皮质病变包含的CD 3阳性淋巴细胞少13倍（195 vs 2，596/mm 3组织），CD 68阳性小胶质细胞/巨噬细胞少6倍（11，948 vs 67，956/mm 3组织）。横断的神经突（轴突和树突）在活动性皮质病变中的密度为4，119/mm（3），在慢性活动性皮质病变中为1，107/mm（3），在慢性非活动性皮质病变中为25/mm（3），在有髓鞘MS皮质中为8/mm（3），在对照皮质中为1/mm（3）。在活动性和慢性活动性皮质病变中，活化的小胶质细胞紧密贴壁并包裹顶端树突、神经突和神经元胞体。此外，与有髓皮质相比，脱髓鞘皮质中凋亡神经元显著增加。这些数据支持这一假设，即脱髓鞘，轴突横断，树突状横断，和神经元的凋亡损失在大脑皮层有助于MS患者的神经功能障碍。
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm(3) of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm(3) of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm(3) in active cortical lesions, 1,107/mm(3) in chronic active cortical lesions, 25/mm(3) in chronic inactive cortical lesions, 8/mm(3) in myelinated MS cortex, and 1/mm(3) in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.