Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3
| Autor: | David Ley, Alex Adusei Agyemang, Norman W. Barton, Bo Holmqvist, Suvi Vallius, Galen Carey, Xiaoyang Wang, Ann Hellström, Lois E.H. Smith, Claes Ekström, Alexandra Mangili, Magnus Gram, William Hellström, Niklas Ortenlöf |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Article Insulin-like growth factor Developmental Neuroscience Downregulation and upregulation Internal medicine Gene expression medicine Animals Humans Insulin-like growth factor-1 system Insulin-Like Growth Factor I Receptor Insulin-like growth factor 1 receptor business.industry Growth factor Infant Newborn Vascular development Brain development Recombinant Proteins Insulin-Like Growth Factor Binding Protein 3 Endocrinology Intraventricular hemorrhage Neurology In utero Infant Extremely Premature Premature Birth Choroid plexus Rabbits Carrier Proteins Prematurity business |
| Zdroj: | Developmental neuroscience |
| ISSN: | 1421-9859 0378-5866 |
| DOI: | 10.1159/000516665 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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