Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.
Dev Neurosci

中文翻译：

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早产兔幼仔中的胰岛素样生长因子 1：重组人胰岛素样生长因子 1/胰岛素样生长因子 1 结合蛋白 3 给药后脑血管成熟的表征

早产后，与相应的子宫内水平相比，胰岛素样生长因子 1 (IGF-1) 的血清水平降低。最近的一项临床试验表明，补充重组人 (rh) IGF-1/rhIGF 结合蛋白 3 (rhIGF-1/rhIGFBP-3) 可预防极早产儿的严重脑室内出血 (IVH)。在早产兔幼犬模型中，我们表征了内源性血清和肝脏 IGF-1，以及 IGF-1 和 IGF-1 受体 (IGF1R) 的脑分布。然后，我们评估了 rhIGF-1/rhIGFBP-3 对脑血管成熟和结构调节因子基因表达的影响。与早产儿相似，兔幼崽早产后血清 IGF-1 浓度迅速下降。rhIGF-1/rhIGFBP-3 的施用恢复了子宫内血清水平，但很快被消除。免疫标记的 IGF1R 广泛分布在多个脑区，在脉络丛和室管膜下生发区显示出丰富的密度。在 rhIGF-1/rhIGFBP-3 给药后 4 小时检测到 IGF-1 免疫反应性增加，分布为 IGF1R。rhIGF-1/rhIGFBP-3 治疗导致参与血管成熟和结构的脉络丛基因上调，其中大多数基因具有相应的蛋白质翻译。早产兔幼崽模型非常适合评估基于 IGF-1 的 IVH 预防。rhIGF-1/rhIGFBP-3 的给药影响脑血管成熟，表明它在预防早产 IVH 中的作用。在 rhIGF-1/rhIGFBP-3 给药后 4 小时检测到。rhIGF-1/rhIGFBP-3 治疗导致参与血管成熟和结构的脉络丛基因上调，其中大多数基因具有相应的蛋白质翻译。早产兔幼崽模型非常适合评估基于 IGF-1 的 IVH 预防。rhIGF-1/rhIGFBP-3 的给药影响脑血管成熟，表明它在预防早产 IVH 中的作用。在 rhIGF-1/rhIGFBP-3 给药后 4 小时检测到。rhIGF-1/rhIGFBP-3 治疗导致参与血管成熟和结构的脉络丛基因上调，其中大多数基因具有相应的蛋白质翻译。早产兔幼崽模型非常适合评估基于 IGF-1 的 IVH 预防。rhIGF-1/rhIGFBP-3 的给药影响脑血管成熟，表明它在预防早产 IVH 中的作用。
开发神经科学