In vivo MRI of endogenous stem/progenitor cell migration from subventricular zone in normal and injured developing brains

In vivo MRI of endogenous stem/progenitor cell migration from subventricular zone in normal and injured developing brains
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正常和受损发育大脑脑室下区内源性干/祖细胞迁移的体内 MRI

DOI:
10.1016/j.neuroimage.2009.06.075
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发表时间:
2009-11-01
期刊:
影响因子:
5.7
通讯作者:
Wu, Ed X.
Wu, Ed X.
中科院分区:
医学1区
文献类型:
--
作者:
Yang, Jian;Liu, Jianxin;Wu, Ed X.

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出于治疗原因,了解受损发育大脑中内源性神经干/祖细胞(NSP)迁移活动的变化变得越来越重要。在这项研究中,出生后第 7 天有或没有缺氧缺血 (HI) 损伤的 10 日龄新生大鼠被脑室内注射微米级氧化铁颗粒 (MPIO),然后在 7 T 下进行连续两周的高分辨率 MRI。 MRI 结果与使用铁染色和几种免疫组织化学双染色的组织学分析相关。结果表明,在正常和HI损伤的大脑中,来自室下区(SVZ)的NSP被MPIO标记,并迁移为新产生的细胞(铁(+)/BrdU(+))、成神经细胞(铁(+)/巢蛋白(+))、星形胶质细胞或星形胶质细胞样祖细胞(铁(+)/GFAP(+))和成熟神经元(铁(+)/NeuN(+))。在正常大脑中,内源性 NSP 主要在头端和尾端方向表现出切向模式。在一些大鼠中可以观察到 NSP 径向迁移模式。在同一发育时期HI损伤的大脑中,NSP主要向HI损伤部位迁移。可以观察到切向、轴尾迁移,但受到损害。这些发现表明,SVZ 中的 NSP 迁移途径会因 HI 损伤而发生变化,这可能是由于新生儿大脑中已知的自我修复工作所致。这里展示的 MRI 方法可能适用于正常和病理条件下发育中的大脑以及治疗干预中 NSP 细胞活动的体内和纵向研究。 (C) 2009 Elsevier Inc. 保留所有权利。
Understanding the alterations of migratory activities of the endogenous neural stem/progenitor cells (NSPs) in injured developing brains is becoming increasingly imperative for curative reasons. In this study, 10-day-old neonatal rats with and without hypoxic-ischemic (HI) insult at postnatal day 7 were injected intraventricularly with micron-sized iron oxide particles (MPIOs), followed by serial high-resolution MRI at 7 T for 2 weeks. MRI findings were correlated to the histological analysis using iron staining and several immunohistochemical double staining. The results indicated that in normal and HI-injured brains the NSPs from the subventricular zone (SVZ) were labeled by MPIOs, and migrated as newly created cells (iron(+)/BrdU(+)), neuroblasts (iron(+)/nestin(+)), astrocytes or astrocytes-like progenitor cells (iron(+)/GFAP(+)), and mature neurons (iron(+)/NeuN(+)). In normal brains, the endogenous NSPs mainly exhibited a tangential pattern in both rostral and caudal directions. The NSP radial migratory pattern could be observed in some rats. In the HI-injured brains during the same developmental period, the NSPs mainly migrated towards the HI lesion sites. The tangential, rostrocaudal migrations could be observed but impaired. These findings suggest that the NSP migratory pathways in SVZ change in response to the HI insult, likely due to the self-repairing efforts known in the neonatal brains. The MRI approach demonstrated here is potentially applicable to the in vivo and longitudinal study of NSP cell activities in developing brains under normal and pathological conditions and in therapeutic interventions. (C) 2009 Elsevier Inc. All rights reserved.