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Published on: June 29, 2013
Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following
Magnus Gram1, Claes Ekström2, Bo Holmqvist3
1Department of Clinical Sciences Lund, Pediatrics, Lund University, Lund, Sweden, magnus.gram@med.lu.se.
Insights
Recombinant human insulin-like growth factor 1/binding protein 3 (rhIGF-1/rhIGFBP-3) supplementation in preterm rabbit pups boosted cerebrovascular maturation. This suggests a potential role for rhIGF-1/rhIGFBP-3 in preventing intraventricular hemorrhage in extremely preterm infants.
Area of Science:
- Neonatal Physiology
- Developmental Biology
- Pharmacology
Background:
- Serum insulin-like growth factor 1 (IGF-1) levels decline significantly following preterm birth compared to in utero levels.
- Recombinant human IGF-1/IGF-binding protein 3 (rhIGF-1/rhIGFBP-3) has shown promise in preventing severe intraventricular hemorrhage (IVH) in extremely preterm infants.
Purpose of the Study:
- To characterize endogenous serum and hepatic IGF-1 and brain distribution of IGF-1 and its receptor (IGF1R) in a preterm rabbit pup model.
- To evaluate the effects of rhIGF-1/rhIGFBP-3 on gene expression regulating cerebrovascular maturation and structure in preterm rabbit pups.
Main Methods:
- Utilized a preterm rabbit pup model to study serum and hepatic IGF-1 levels and brain distribution of IGF-1 and IGF1R.
- Administered rhIGF-1/rhIGFBP-3 and assessed its impact on gene expression related to cerebrovascular development.
- Quantified IGF-1 and IGF1R distribution via immunolabeling in various brain regions.
Main Results:
- Serum IGF-1 concentrations decreased post-preterm birth in rabbit pups, mirroring human infant patterns.
- rhIGF-1/rhIGFBP-3 administration restored serum IGF-1 levels, though it was rapidly eliminated.
- IGF1R was widely distributed in the brain, particularly in the choroid plexus and sub-ependymal germinal zones. rhIGF-1/rhIGFBP-3 upregulated choroid plexus genes involved in vascular maturation and structure.
Conclusions:
- The preterm rabbit pup model is suitable for investigating IGF-1-based IVH prevention strategies.
- rhIGF-1/rhIGFBP-3 administration positively influences cerebrovascular maturation, indicating its potential therapeutic role in preventing IVH in preterm neonates.
Abstract:
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.
