IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia-ischemia in the neonatal rat
IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia-ischemia in the neonatal rat
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DOI：
10.1016/j.brainres.2005.09.042
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发表时间：
2005-11-23
期刊：
影响因子：
2.9
通讯作者：
Cai, ZW
中科院分区：
文献类型：
--
作者：
Lin, SY;Fan, LW;Cai, ZW
为了研究胰岛素样生长因子-1 （IGF-1）是否对脑缺氧缺血后的少突胶质细胞祖细胞（OPCs）提供神经保护，本研究使用了先前建立的新生大鼠白质损伤模型。出生后第4天（P4） SD大鼠幼仔进行双侧颈总动脉结扎，随后暴露于8%的氧气中10分钟。在动脉结扎后和缺氧暴露前向左心室注射IGF-1 （0.5 μ g）或对照物。脑缺氧缺血导致P5大鼠脑O4+晚期OPCs死亡，P9和P21大鼠脑髓鞘形成受损。Caspase-3激活参与了OPCs的死亡。此外，脑缺氧缺血会损害幼年大鼠的神经行为表现。IGF-1治疗可减轻脑缺氧缺血后OPCs的损伤并改善神经功能。它使O4+ OPCs在P5时的死亡率降低39%，并增强P9和P21时的髓鞘形成。溴脱氧尿苷摄取实验显示，脑缺氧缺血抑制脑室下区干/祖细胞增殖和白质区NG2+早期OPCs增殖。缺氧缺血性损伤后1天，IGF-1治疗使室下区细胞增殖增加31%。igf -1处理组早期和晚期OPCs的增殖分别是载体处理组的1.5倍和2.4倍。综上所述，IGF-1对新生大鼠脑缺氧缺血后的OPCs具有有效的神经保护作用，并能改善其神经功能。IGF-1的神经保护作用与其抗凋亡和有丝分裂作用有关。(c) 2005 Elsevier B.V.版权所有
To investigate if insulin-like growth factor-1 (IGF-1) provides neuroprotection to oligodendrocyte progenitor cells (OPCs) following cerebral hypoxia-ischemia, a previously developed neonatal rat model of white matter damage was used in this study. Postnatal day 4 (P4) SD rat pups were subjected to bilateral common carotid artery ligation, followed by exposure to 8% oxygen for 10 min. IGF-1 (0.5 mu g) or vehicle was injected into the left ventricle after artery ligation and before the hypoxic exposure. Cerebral hypoxia-ischemia caused death of O4+ late OPCs in the P5 rat brain and impaired myelination in the P9 and P21 rat brain. Caspase-3 activation was involved in the death of OPCs. Moreover, cerebral hypoxia-ischemia impaired neurobehavioral performance in juvenile rats. IGF-1 treatment attenuated damages to OPCs and improved neurological functions after cerebral hypoxia-ischemia. It reduced death of O4+ OPCs by 39% on P5 and enhanced myelination on P9 and P21. Bromodeoxyuridine uptake assay showed that cerebral hypoxia-ischemia inhibited proliferation of stem/progenitor cells in the subventricular zone and NG2+ early OPCs in the white matter area. IGF-1 treatment increased cell proliferation in the subventricular zone by 31% 1 day following hypoxic-ischemic insult. Proliferation of early and late OPCs in the IGF-1-treated group was 1.5- and 2.4-fold of that in the vehicle-treated group, respectively. In conclusion, IGF-1 provided potent neuroprotection to OPCs and improved neurological functions following cerebral hypoxia-ischemia in the neonatal rat. The neuroprotection of IGF-1 was associated with its antiapoptotic and mitogenic effects. (c) 2005 Elsevier B.V. All rights reserved.