Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models.
Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models.
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DOI：
10.1007/s00401-014-1263-5
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发表时间：
2014-08
影响因子：
12.7
通讯作者：
Lassmann H
中科院分区：
文献类型：
--
作者：
Schuh C;Wimmer I;Hametner S;Haider L;Van Dam AM;Liblau RS;Smith KJ;Probert L;Binder CJ;Bauer J;Bradl M;Mahad D;Lassmann H
最近的数据表明，氧化损伤可能在多发性硬化症(MS)的脱髓鞘和神经退行性变中发挥重要作用。我们比较了MS损伤和由不同炎症机制驱动的实验模型中氧化损伤的程度。只有在冠状病毒诱导的脱髓鞘脑脊髓炎模型中，我们检测到氧化磷脂的积累，其程度与MS和冠状病毒诱导的脑脊髓炎的程度相当，这与MS和冠状病毒诱导的脑脊髓炎有关，这与小胶质细胞和巨噬细胞的大量激活有关，并伴随着NADPH氧化酶亚基p22Phox的表达，但仅有少量的诱导型一氧化氮合酶(INOS)的表达。急性和慢性CD4+T细胞介导的实验性自身免疫性脑脊髓炎病变显示p22Phox和iNOS的瞬时表达与炎症相关。抗体介导的脱髓鞘脑脊髓炎慢性病变的巨噬细胞表现出溶酶体活性，但p22Phox或iNOS的表达很少。CD8+T细胞或天然免疫诱导的活动性炎性脱髓鞘病变表现为巨噬细胞和小胶质细胞活化，并伴有p22Phox的表达，但iNOS活性低或缺失。我们通过基因表达研究证实了急性CD4+T细胞介导的实验性自身免疫性脑脊髓炎和急性多发性硬化症病变之间的差异。此外，与年龄相关的铁积累和损伤相关的铁释放，就像在人脑中发生的那样，在啮齿类动物的大脑中只是很小的。我们的研究表明，氧化损伤及其触发机制在不同的啮齿动物中枢神经系统炎症模型中存在差异。氧化损伤的放大在MS中已被提出，但在所研究的啮齿动物模型中仅有有限程度的反映。本文的在线版本(doi：10.1007/s00401-014-1263-5)包含补充材料，授权用户可以使用。
Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4+ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8+ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4+ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models. The online version of this article (doi:10.1007/s00401-014-1263-5) contains supplementary material, which is available to authorized users.
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影响因子：
3.4
作者：
Fonseca-Kelly Z;Nassrallah M;Uribe J;Khan RS;Dine K;Dutt M;Shindler KS
通讯作者：
Shindler KS
影响因子：
4.7
作者：
Choi SH;Aid S;Kim HW;Jackson SH;Bosetti F
通讯作者：
Bosetti F
影响因子：
4.7
作者：
Dasgupta A;Zheng J;Perrone-Bizzozero NI;Bizzozero OA
通讯作者：
Bizzozero OA
DOI：
10.1093/brain/aws012
发表时间：
2012-03
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Fischer MT;Sharma R;Lim JL;Haider L;Frischer JM;Drexhage J;Mahad D;Bradl M;van Horssen J;Lassmann H
通讯作者：
Lassmann H
影响因子：
12.7
作者：
Aboul-Enein, F;Weiser, P;Bradl, M
通讯作者：
Bradl, M