Stem cell dynamics in an experimental model of stroke.
Stem cell dynamics in an experimental model of stroke.
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DOI：
10.4068/cmj.2011.47.2.90
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Woo YJ
中科院分区：
文献类型：
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作者：
Lee MC;Jin CY;Kim HS;Kim JH;Kim MK;Kim HI;Lee YJ;Son YJ;Kim YO;Woo YJ
我们研究了内源性神经干细胞（NSCs）向梗死灶的光血栓性中风模型的迁移。还通过30分钟至8周的连续磁共振成像（MRI）评价了在Sprague-Dawley大鼠运动皮层中使用虎红染料（20 mg/kg）和冷光产生的病变。巢蛋白单克隆抗体免疫组化法检测神经干细胞在损伤皮质、脑室下区（SVZ）和胼胝体（CC）的迁移。在DWI中，MRI的对比与非对比比率（CNR）在12小时时最大，并随时间推移而降低。相比之下，T1加权和T2加权图像显示从开始到8周恒定的CNR。病变皮质的MRI与组织病理学结果相关，可分为3个阶段：24小时内的急性（水肿和坏死），2 - 7天的亚急性（急性和慢性炎性细胞浸润）和2 - 4周的慢性（胶质纤维化）。修复性胶质纤维化显著缩小梗死体积。各组对侧SVZ中nestin+ NSCs的数量与同侧SVZ中nestin+ NSCs的数量相似。而同侧皮质和CC中nestin+ NSCs的数量在12 h ~ 3 d较对侧增加（p<0.01），7 d时明显减少（p<0.01）。内部神经干细胞从SVZ向梗死灶的主动迁移也可能有助于梗死灶体积的减小，但内源性神经干细胞的自我修复机制不足以治疗引起广泛神经元死亡的卒中。今后应加强对神经干细胞扩增技术的研究，以提高内源性或移植性神经干细胞治疗脑卒中的效果。
We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.