Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat

Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat
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DOI:
10.1016/j.neuroscience.2004.10.011
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发表时间:
2005-01-01
期刊:
影响因子:
3.3
通讯作者:
Tator, CH
Tator, CH
中科院分区:
医学3区
文献类型:
--
作者:
Mothe, AJ;Tator, CH

文献摘要

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成年哺乳动物脊髓的室管膜细胞在损伤后表现出干/祖细胞特性。在本研究中,我们利用脑室内注射 1,1'-双十八烷基-6,6'-二(4-磺基苯基)-3,3,3',3'-四甲基吲哚羰花青 (Dil) 来标记中央管内的室管膜,以跟踪脊髓损伤 (SCI) 后内源性室管膜细胞及其后代的迁移。我们开发了一种最小损伤模型,可以保留中央管的完整性,并且不会干扰室管膜细胞标记。 SCI 三天后,根据溴脱氧尿苷标记,与损伤后 1 天相比,针迹水平的室管膜细胞增殖标记指数增加了 8.6 倍。在室管膜或周围灰质中未检测到末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 阳性细胞,表明室管膜细胞不会因轻微损伤而发生凋亡。巢蛋白在 1 天时在室管膜中迅速诱导,并在损伤后 7 天表达达到峰值。我们定量了最小损伤后室管膜细胞迁移的数量和距离。轻微损伤后3天,从中央管区域迁移的室管膜细胞数量增加,SCI后114天检测到Dil标记的胶质纤维酸性蛋白表达细胞,其中大部分迁移到中央管区域70μm以内。这些结果表明,邻近室管膜的最小 SCI 足以诱导内源性室管膜细胞反应,其中室管膜干/祖细胞增殖并从中央管区域迁移,主要分化为星形胶质细胞。 (C) 2004 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Ependymal cells of the adult mammalian spinal cord exhibit stem/progenitor cell properties following injury. In the present study, we utilized intraventricular injection of 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3,3',3'-tetramethylindocarbocyanine (Dil) to label the ependyma lining the central canal to allow tracking of the migration of endogenous ependymal cells and their progeny after spinal cord injury (SCI). We developed a minimal injury model that preserved the integrity of the central canal and did not interfere with ependymal cell labeling. Three days following SCI, there was an 8.6-fold increase in the proliferative labeling index of the ependymal cells at the level of the needle track based on bromodeoxyuridine labeling, compared with 1 day post-injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells were not detected in the ependyma or surrounding gray matter, indicating that ependymal cells do not undergo apoptosis in response to minimal injury. Nestin was rapidly induced in the ependyma by 1 day and expression peaked by 7 days post-injury. We quantitated the number and distance of ependymal cell migration following minimal injury. The number of ependymal cells migrating from the region of the central canal increased by 3 days following minimal injury and Dil-labeled glial fibrillary acidic protein expressing cells were detected 114 days post-SCI, most of which migrated within 70 mum of the region of the central canal. These results show that a minimal SCI adjacent to the ependyma is sufficient to induce an endogenous ependymal cell response where ependymal stem/progenitor cells proliferate and migrate from the region of the central canal, differentiating primarily into astrocytes. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.