Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats
Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats
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DOI：
10.1007/s00441-012-1538-x
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发表时间：
2013-03-01
影响因子：
3.6
通讯作者：
Lee, Mun-Yong
中科院分区：
文献类型：
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作者：
Shin, Yoo-Jin;Kim, Hong Lim;Lee, Mun-Yong
本研究的目的是提供一个详细的表征的细胞表型的巢蛋白阳性细胞在大鼠缺血性中风模型。巢蛋白阳性细胞包括梗死周围区域的反应性星形胶质细胞。在缺血的核心，其中星形胶质细胞几乎消失，巢蛋白的表达是专门与血管，包括微血管和大口径血管。诱导巢蛋白表达在缺血核心缺血后3天发生。巢蛋白表达持续到缺血后至少28天，但巢蛋白阳性细胞的细胞分布在此期间发生变化。在第3天的缺血核心，巢蛋白阳性细胞经常有长的进程，运行平行沿着血管的纵轴。这些细胞高度增殖，并表达神经/神经胶质祖细胞的转录因子Sox 9。基于其形态学特征和双标记研究，大多数nestin阳性细胞与血管相关细胞（包括内皮细胞、平滑肌细胞和小胶质细胞/巨噬细胞）可清楚区分。免疫电镜结果表明，大多数巢蛋白阳性细胞位于血管周围的空间，并有巨噬细胞样功能，表明形态相似的血管周围巨噬细胞。缺血14天后，巢蛋白表达仍与血管有关，但出现在成纤维细胞样细胞中。因此，我们的数据表明，在缺血的核心，巢蛋白的表达不仅限于祖细胞/干细胞群体，但在血管相关细胞诱导。这些细胞类型包括血管周围巨噬细胞和成纤维细胞样细胞，似乎经历动态结构变化。这些结果表明，巢蛋白促进细胞结构重塑，缺血性损伤的反应。
The present study aimed to provide a detailed characterization of the cellular phenotypes of nestin-positive cells in a rat model of ischemic stroke. Nestin-positive cells included reactive astrocytes in the peri-infarct region. In the ischemic core, in which astrocytes had virtually disappeared, nestin expression was exclusively associated with the vasculature, including the microvasculature and larger caliber vessels. Induction of nestin expression in the ischemic core occurred by 3 days post-ischemia. Nestin expression continued through at least 28 days post-ischemia but the cellular profiles of nestin-positive cells changed over this period. In the ischemic core at day 3, nestin-positive cells frequently had long processes that ran parallel along the longitudinal axis of the vasculature. These cells were highly proliferative and expressed the transcription factor for neural/glial progenitors, Sox9. Based on their morphological characteristics and on a double-labeling study, most nestin-positive cells were clearly distinguishable from vasculature-associated cells including endothelial cells, smooth muscle cells and microglia/macrophages. Immunoelectron microscopic findings demonstrated that most nestin-positive cells lay in the perivascular space and had macrophage-like features, indicating morphological similarity to perivascular macrophages. Nestin expression was still associated with the vasculature 14 days after ischemia but appeared in fibroblast-like cells. Thus, our data indicated that, in the ischemic core, nestin expression was not limited to a progenitor/stem cell population but was induced in the vasculature-associated cells. These cell types included perivascular macrophages and fibroblast-like cells that appeared to undergo dynamic structural changes. These results suggest that nestin facilitates cellular structural remodeling in response to ischemic injury.