Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury
Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury
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DOI：
10.1016/s0169-328x(98)00122-3
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发表时间：
1998-08-31
期刊：
影响因子：
--
通讯作者：
Scheepens, A
中科院分区：
文献类型：
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作者：
Beilharz, EJ;Russo, VC;Scheepens, A
胰岛素样生长因子1（IGF-1）诱导缺氧缺血性脑损伤后，治疗研究表明，IGF-1可以限制迟发性神经元和胶质细胞的损失。我们已经使用了一个良好的特点，HI损伤大鼠模型，以扩大我们的理解，损伤后的IGF系统的作用模式。采用原位杂交、免疫组化、北方印迹分析、RNA酶保护试验和逆转录聚合酶链反应（RT-PCR）检测损伤对IGF系统的诱导作用。IGF-1在严重损伤后5小时内在受损半球的血管中积累。到3天，IGF-1 mRNA表达的反应性小胶质细胞在迟发性神经元死亡的地区，和免疫反应性IGF-1与这些小胶质细胞和反应性星形胶质细胞并列存活的神经元周围的梗死。总IGF-1受体mRNA的损伤不变。IGFBP-2 mRNA在整个损伤半球的反应性星形胶质细胞中被强烈诱导，IGFBP-3和IGFBP-5 mRNA分别在损伤海马的反应性小胶质细胞和神经元中被中度诱导。IGFBP-6 mRNA在受损半球诱导3天，脉络丛，室管膜和反应性胶质细胞上的蛋白质增加。相反，胰岛素II未被诱导。这些结果表明损伤后IGF-1、IGFBP-2、3、5和6的细胞类型特异性表达。我们的研究结果表明，小胶质细胞损伤后产生的IGF-1转移到神经元周反应性星形胶质细胞表达IGFBP-2。因此，IGFBP-2对IGF-1作用的调节可能是限制HI脑损伤后神经元细胞丢失的关键机制。(C)1998 Elsevier Science B. V.保留所有权利。
Insulin-like growth factor 1 (IGF-1) is induced after hypoxic-ischemic (HI) brain injury, and therapeutic studies suggest that IGF-1 may restrict delayed neuronal and glial cell loss. We have used a well-characterised rat model of HI injury to extend our understanding of the modes of action of the IGF system after injury. The induction of the IGF system by injury was examined by in situ hybridization, immunohistochemistry, Northern blot analysis, RNase protection assay and reverse transcriptase-polymerase chain reaction (RT-PCR). IGF-1 accumulated in blood vessels of the damaged hemisphere within 5 h after a severe injury. By 3 days, IGF-1 mRNA was expressed by reactive microglia in regions of delayed neuronal death, and immunoreactive IGF-1 was associated with these microglia and reactive astrocytes juxtaposed to surviving neurones surrounding the infarct. Total IGF-1 receptor mRNA was unchanged by the injury. IGFBP-2 mRNA was strongly induced in reactive astrocytes throughout the injured hemisphere, and IGFBP-3 and IGFBP-5 mRNA were moderately induced in reactive microglia and neurones of the injured hippocampus, respectively. IGFBP-6 mRNA was induced in the damaged hemisphere by 3 days and increased protein was seen on the choroid plexus, ependyma and reactive glia. In contrast, insulin II was not induced. These results indicate cell type-specific expression for IGF-1, IGFBP-2,3,5 and 6 after injury. Our findings suggest that the IGF-1 produced by microglia after injury is transferred to perineuronal reactive astrocytes expressing IGFBP-2. Thus, modulation of IGF-1 action by IGFBP-2 might represent a key mechanism that restricts neuronal cell loss following HI brain injury. (C) 1998 Elsevier Science B.V. All rights reserved.