Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near-term fetal sheep
Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near-term fetal sheep
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DOI：
10.1097/01.wcb.0000067720.12805.6f
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发表时间：
2003-06-01
影响因子：
6.3
通讯作者：
Guan, J
中科院分区：
文献类型：
--
作者：
Cao, Y;Gunn, AJ;Guan, J
胰岛素样生长因子（IGF-1）显著增加近期胎羊缺血后白质髓鞘和胶质细胞数量；然而，尚不清楚这是由于细胞损失减少还是继发性增殖增加。用双侧颈动脉闭塞30分钟的方法对近期胎羊进行脑损伤。阻断90分钟后，胎儿在脑室内注射单剂量的IGF-1（3杯或30杯），或3杯后再注射3杯24小时（3 + 3杯）。再灌注4天后评估白质。与对照组相比，3微克的IGF-1，而不是30杯的IGF-1，可以防止少突胶质细胞和髓鞘碱性蛋白密度的损失（P < 0.001）。3 + 3杯子组没有观察到额外的效果。IGF-1治疗与caspase-3激活降低和胶质细胞增殖增加相关，并以类似的剂量依赖方式相关。Caspase-3仅在呈现凋亡形态的少突胶质细胞中表达。增殖细胞核抗原与少突胶质细胞、星形胶质细胞和小胶质细胞共定位。因此，IGF-I处理后少突胶质细胞数量的增加部分是由于抑制凋亡，部分是由于增殖增加。相反，反应性胶质细胞的增加只与增殖有关。推测，反应性胶质细胞可能部分介导IGF-1白质保护。
Insulin-like growth factor (IGF-1) markedly increases myelination and glial numbers in white matter after ischernia in near-term fetal sheep; however, it is unclear whether this is due to reduced cell loss or increased secondary proliferation. Brain injury was induced in near-term fetal sheep by 30 minutes of bilateral carotid artery occlusion. Ninety minutes after the occlusion, fetuses were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or 30 mug), or 3 mug followed by 3 mug over 24 hours (3 + 3 mug). White matter was assessed 4 days after reperfusion. Three micrograms, but not 30 mug of IGF-1 prevented loss of oligodendrocytes and myelin basic protein density (P < 0.001) compared to the vehicle-treated ischernia controls. No additional effect was observed in the 3 + 3 mug group. IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner. Caspase-3 was only expressed in oligodendrocytes that showed apoptotic morphology. Proliferating cell nuclear antigen co-localized with both oligodendrocytes and astrocytes and microglia. Thus, increased oligodendrocyte numbers after IGF-I treatment is partly due to suppression of apoptosis, and partly to increased proliferation. In contrast, the increase in reactive glia was related only to proliferation. Speculatively, reactive glia may partly mediate IGF-1 white matter protection.