Remyelination can be extensive in multiple sclerosis despite a long disease course

Remyelination can be extensive in multiple sclerosis despite a long disease course
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DOI:
10.1111/j.1365-2990.2007.00805.x
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发表时间:
2007-06-01
影响因子:
5
通讯作者:
Reynolds, R.
Reynolds, R.
中科院分区:
医学2区
文献类型:
--
作者:
Patani, R.;Balaratnam, M.;Reynolds, R.

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使用多发性硬化(MS)模型的实验研究表明,炎症性脱髓鞘病变的快速和广泛的髓鞘再生不仅是可能的,而且是正常情况。在许多研究中已经注意到完全髓鞘再生的MS病变的存在,并且死后MS材料的常规有限采样表明髓鞘再生在早期阶段可能是广泛的,但最终失败。然而,肉眼可见的引导取样往往偏向于慢性脱髓鞘病变。在这里,我们从两个多发性硬化症病例中广泛取样脑组织,以调查髓鞘再生的真实程度。从185个脑组织块中切下切片,并用苏木素和伊红(H&E)、luxol固蓝和甲苯基固紫(LFB/CFV)以及抗髓鞘少突胶质细胞糖蛋白、人白细胞抗原DR(HLA-DR)和200 kDa神经丝蛋白抗体染色。在141个组织块中识别出脱髓鞘区域,包括白色物质(WML)和/或灰质病变。总共鉴定了168个WML,其中22%为阴影斑块,73%为部分髓鞘再生,仅5%为完全脱髓鞘。所有研究的WML损伤髓鞘再生的平均程度为47%。病灶边缘HLA-DR+巨噬细胞和小胶质细胞密度增加与更广泛的髓鞘再生显著相关。这项对两名长期患病患者的研究结果表明,MS的髓鞘再生可能比以前认为的更广泛。
Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR+ macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought.