Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis
Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis
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DOI：
10.1056/nejmoa010994
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发表时间：
2002-01-17
影响因子：
158.5
通讯作者：
Trapp, BD
中科院分区：
文献类型：
--
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
背景：多发性硬化是一种中枢神经系统的炎症性疾病，会破坏髓鞘、少突胶质细胞和轴突。由于多发性硬化的大多数病变无法重新髓鞘化，增强重新髓鞘化可能是一种治疗策略，也许可以通过将产生少突胶质细胞的细胞移植到病变部位来实现。我们研究了多发性硬化慢性病变中少突胶质细胞的频率分布和形态，以确定这些因素是否限制了重新髓鞘化。
方法：对10例多发性硬化患者尸检获得的48个慢性病变进行少突胶质细胞和少突胶质细胞祖细胞的免疫细胞化学检查。利用共聚焦显微镜，我们检查了轴突与髓鞘形成前少突胶质细胞突起之间的三维关系。
结果：48个多发性硬化慢性病变中有34个含有少突胶质细胞，这些细胞有多个延伸的突起，与脱髓鞘的轴突相关联，但未能使它们髓鞘化。这些轴突营养不良，含有多个肿胀部位。在一些区域，髓鞘形成前少突胶质细胞的密度（每平方毫米组织25个）与发育中的啮齿动物大脑中的密度（每平方毫米23个）相似。在病程较长（超过20年）的患者中，含有髓鞘形成前少突胶质细胞的病变较少（P<0.05）。
Background: Multiple sclerosis is an inflammatory disease of the central nervous system that destroys myelin, oligodendrocytes, and axons. Since most of the lesions of multiple sclerosis are not remyelinated, enhancement of remyelination is a possible therapeutic strategy that could perhaps be achieved with the transplantation of oligodendrocyte-producing cells into the lesions. We investigated the frequency distribution and configuration of oligodendrocytes in chronic lesions of multiple sclerosis to determine whether these factors limit remyelination.Methods: Forty-eight chronic lesions obtained at autopsy from 10 patients with multiple sclerosis were examined immunocytochemically for oligodendrocytes and oligodendrocyte progenitor cells. Using confocal microscopy, we examined the three-dimensional relations between axons and the processes of premyelinating oligodendrocytes.Results: Thirty-four of the 48 chronic lesions of multiple sclerosis contained oligodendrocytes with multiple extended processes that associated with demyelinated axons but failed to myelinate them. These axons were dystrophic and contained multiple swellings. In some regions, the densities of premyelinating oligodendrocytes (25 per square millimeter of tissue) were similar to those in the developing rodent brain (23 per square millimeter). In the patients with disease of long duration (more than 20 years), there were fewer lesions with premyelinating oligodendrocytes (P