Cortical remyelination: a new target for repair therapies in multiple sclerosis.
Cortical remyelination: a new target for repair therapies in multiple sclerosis.
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DOI：
10.1002/ana.23693
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发表时间：
2012-12
影响因子：
11.2
通讯作者：
Trapp, Bruce D.
中科院分区：
文献类型：
--
作者：
Chang, Ansi;Staugaitis, Susan M.;Dutta, Ranjan;Batt, Courtney E.;Easley, Kathryn E.;Chomyk, Anthony M.;Yong, V. Wee;Fox, Robert J.;Kidd, Grahame J.;Trapp, Bruce D.
在脱髓鞘的白色物质中新的少突胶质细胞的产生和分化是成人大脑中最好描述的修复过程。然而，多发性硬化症患者的髓鞘再生能力随着年龄的增长而减弱。（MS）。由于大脑皮层脱髓鞘在MS患者的大脑中广泛存在，因此我们研究了皮质病变髓鞘再生的能力，并直接比较了涉及大脑皮层和相邻皮质下白色物质的病变髓鞘再生的程度。分析了22例MS患者（年龄27至77岁）和6例无脑部疾病的受试者的尸检脑组织。对髓鞘减少的大脑皮层区域进行髓鞘再生、少突胶质细胞祖细胞、反应性星形胶质细胞和抑制髓鞘再生的分子检查。在30/42个有髓鞘再生的软膜下皮质病变中鉴定出活跃形成髓鞘的“新”少突胶质细胞，包括来自三名70多岁患者的病变。与相邻的正常皮质或对照组相比，脱髓鞘或髓鞘再生皮质中的少突胶质祖细胞没有减少。在涉及皮质和邻近白色物质的脱髓鞘病变中，皮质表现出更大的髓鞘再生，更活跃的髓鞘再生少突胶质细胞和更少的反应性星形胶质细胞。白质中的星形胶质细胞，而不是在这些病变的皮质部分，显着上调CD 44，透明质酸，和多功能蛋白聚糖，形成复合物，抑制少突胶质细胞成熟和髓鞘再生的分子。无论患者的病程或实际年龄如何，MS患者的大脑皮质都发生内源性髓鞘再生。皮质髓鞘再生应被认为是未来临床试验测试髓鞘再生疗法的主要结局指标。
Generation and differentiation of new oligodendrocytes in demyelinated white matter is the best described repair process in the adult human brain. However, remyelinating capacity falters with age in patients with multiple sclerosis. (MS). Since demyelination of cerebral cortex is extensive in brains from MS patients, we investigated the capacity of cortical lesions to remyelinate and directly compared the extent of remyelination in lesions that involve cerebral cortex and adjacent subcortical white matter. Postmortem brain tissue from 22 patients with MS (age 27 to 77 years) and 6 subjects without brain disease were analyzed. Regions of cerebral cortex with reduced myelin were examined for remyelination, oligodendrocyte progenitor cells, reactive astrocytes, and molecules that inhibit remyelination. “New” oligodendrocytes that were actively forming myelin sheaths were identified in 30/42 remyelinated subpial cortical lesions, including lesions from three patients in their 70's. Oligodendrocyte progenitor cells were not decreased in demyelinated or remyelinated cortices when compared to adjacent normal-appearing cortex or controls. In demyelinated lesions involving cortex and adjacent white matter, the cortex showed greater remyelination, more actively remyelinating oligodendrocytes and fewer reactive astrocytes. Astrocytes in the white-matter, but not in cortical portions of these lesions, significantly up-regulate CD44, hyaluronan, and versican, molecules that form complexes that inhibit oligodendrocyte maturation and remyelination. Endogenous remyelination of the cerebral cortex occurs in individuals with MS regardless of disease duration or chronological age of the patient. Cortical remyelination should be considered as a primary outcome measure in future clinical trials testing remyelination therapies.
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影响因子：
11.2
作者：
PRINEAS, JW;BARNARD, RO;CHO, ES
通讯作者：
CHO, ES
影响因子：
6.4
作者：
Albert, Monika;Antel, Jack;Stadelmann, Christine
通讯作者：
Stadelmann, Christine
影响因子：
11.2
作者：
Peterson, JW;Bö, L;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
DOI：
10.1093/jnen/62.7.723
发表时间：
2003-07-01
影响因子：
3.2
作者：
Bo, L;Vedeler, CA;Mork, SJ
通讯作者：
Mork, SJ