Isolation of locally derived stem/progenitor cells from the peri-infarct area that do not migrate from the lateral ventricle after cortical stroke.
Isolation of locally derived stem/progenitor cells from the peri-infarct area that do not migrate from the lateral ventricle after cortical stroke.
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DOI：
10.1161/strokeaha.110.589010
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发表时间：
2010-09
期刊：
影响因子：
8.3
通讯作者：
Spees JL
中科院分区：
文献类型：
--
作者：
Shimada IS;Peterson BM;Spees JL
涉及皮层和纹状体的中风后，神经发生可由室下区（SVZ）的神经干/祖细胞产生。然而，是否所有类型的中风和不同大小的中风都会激活 SVZ 生态位的神经发生尚存在争议。与皮质/纹状体中风相反，轻度皮质中风后的修复和重塑可能在更大程度上涉及局部皮质干/祖细胞和来自非神经源性微环境的细胞。我们比较了由远端大脑中动脉闭塞（dMCAO）产生的局灶性皮质中风和由腔内缝合模型产生的皮质/纹状体中风后的干/祖细胞反应。为了标记从 SVZ 迁移的神经母细胞，我们在 dMCAO 后将 DiI 注射到侧脑室。通过免疫组织化学，我们对梗塞周围区域表达干细胞/祖细胞标记物的细胞进行了表征。我们从 dMCAO 后的梗塞周围区域分离了皮质干/祖细胞，并测定了它们的自我更新和分化能力。与皮质/纹状体中风相反，局灶性皮质中风不会诱导 dMCAO 后神经母细胞从 SVZ 迁移到梗塞区。通过免疫组织化学，我们观察到梗塞周围区域的反应性星形胶质细胞亚群，它们共同表达放射状胶质细胞标记物，例如 Sox2、Nestin 和 RC2。 dMCAO 后从梗死周围区域克隆分离的神经球分化为神经元、星形胶质细胞、少突胶质细胞和平滑肌细胞。值得注意的是，从梗死周围区域分离的神经球在分化之前也表达 RC2。不穿透纹状体的轻度皮质中风会激活局部皮质干/祖细胞，但不会诱导神经母细胞从 SVZ 生态位迁移。
Neurogenesis can arise from neural stem/progenitor cells of the subventricular zone (SVZ) after strokes involving both the cortex and striatum. However, it is controversial whether all types of stroke and strokes of different sizes activate neurogenesis from the SVZ niche. In contrast with cortical/striatal strokes, repair and remodeling after mild cortical strokes may involve to a greater extent local cortical stem/progenitor cells and cells from non-neurogenic niches. We compared stem/progenitor cell responses after focal cortical strokes produced by distal Middle Cerebral Artery Occlusion (dMCAO) and cortical/striatal strokes produced by the intraluminal suture model. To label migrating neuroblasts from the SVZ, we injected DiI to the lateral ventricle after dMCAO. By immunohistochemistry, we characterized cells expressing stem/progenitor cell markers in the peri-infarct area. We isolated cortical stem/progenitor cells from the peri-infarct area following dMCAO and assayed their self-renewal and differentiation capacity. In contrast with cortical/striatal strokes, focal cortical strokes did not induce neuroblast migration from the SVZ to the infarct zone following dMCAO. By immunohistochemistry, we observed sub-populations of reactive astrocytes in the peri-infarct area that co-expressed radial glial cell markers such as Sox2, Nestin, and RC2. Neural spheres clonally-isolated from the peri-infarct area after dMCAO differentiated into neurons, astrocytes, oligodendrocytes, and smooth muscle cells. Notably, neural spheres isolated from the peri-infarct area also expressed RC2 prior to differentiation. Mild cortical strokes that do not penetrate the striatum activate local cortical stem/progenitor cells but do not induce neuroblast migration from the SVZ niche.