Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mol Cell Neurosci. 1992 Feb;3(1):36-43. doi: 10.1016/1044-7431(92)90006-n.
Insulin-like growth factors-I and -II (IGF-I and -II) and their receptors are present in the central nervous system but their role in brain function is unknown. To elucidate this issue, we investigated the cellular pattern of expression for IGF-I and -II, their receptors, and binding proteins using in situ hybridization and immunocytochemistry in the setting of experimental focal cortical ischemia. There was a striking increase in both IGF-I and IGF-II gene expression in the ischemic cerebral cortex, but the two mRNAs were found in different cell populations. IGF-I mRNA was localized in reactive astrocytes that also stained intensely for glial fibrillary acidic protein (GFAP). IGF-II mRNA and immunoreactivity were contained in activated macrophages, which were highly abundant in the infarct zone and also in the meninges, blood vessels, and choroid plexus of the ischemic brain. High levels of IGF binding protein 2 mRNA were colocalized with IGF-II in these activated macrophages. Type-I IGF receptor mRNA was widely distributed in the affected area and type-II IGF receptor mRNA was also widely expressed but was particularly concentrated in macrophages. These findings suggest that the IGFs are involved in the brain's inflammatory response to injury, with IGF-I expressed by reactive astrocytes and IGF-II by activated macrophages. Their function in this setting is still unknown, but appears likely to be linked to the increased metabolic requirements associated with active phagocytosis.
胰岛素样生长因子-I 和 -II（IGF-I 和 -II）及其受体存在于中枢神经系统中，但它们在大脑功能中的作用尚不清楚。为了阐明这个问题，我们使用原位杂交和免疫细胞化学技术，在实验性大脑皮质局部缺血的情况下，研究了 IGF-I 和 -II、其受体和结合蛋白的细胞表达模式。在缺血性大脑皮质中，IGF-I 和 IGF-II 基因表达都明显增加，但这两种 mRNA 存在于不同的细胞群体中。IGF-I mRNA 定位于反应性星形胶质细胞，这些细胞也强烈表达神经胶质纤维酸性蛋白（GFAP）。IGF-II mRNA 和免疫反应性存在于活化的巨噬细胞中，这些巨噬细胞在梗死区高度丰富，也存在于缺血性大脑的脑膜、血管和脉络丛中。高水平的 IGF 结合蛋白 2 mRNA 与这些活化的巨噬细胞中的 IGF-II 共定位。I 型 IGF 受体 mRNA 在受影响的区域广泛分布，II 型 IGF 受体 mRNA 也广泛表达，但特别集中在巨噬细胞中。这些发现表明，IGFs 参与了大脑对损伤的炎症反应，反应性星形胶质细胞表达 IGF-I，活化的巨噬细胞表达 IGF-II。它们在这种情况下的功能尚不清楚，但似乎与主动吞噬作用相关的代谢需求增加有关。
