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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

Gram, Magnus LU orcid ; Ekström, Claes LU orcid ; Holmqvist, Bo ; Carey, Galen ; Wang, Xiaoyang ; Vallius, Suvi LU ; Hellström, William ; Ortenlöf, Niklas LU ; Agyemang, Alex Adusei LU and Smith, Lois E.H. , et al. (2021) In Developmental Neuroscience 43(5). p.281-295
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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain development, Insulin-like growth factor-1 system, Intraventricular hemorrhage, Prematurity, Vascular development
in
Developmental Neuroscience
volume
43
issue
5
pages
15 pages
publisher
Karger
external identifiers
  • scopus:85110167376
  • pmid:34218224
ISSN
0378-5866
DOI
10.1159/000516665
language
English
LU publication?
yes
id
04b71253-57d7-4014-aaa7-2f8448ed8bc5
date added to LUP
2022-03-03 16:57:17
date last changed
2024-04-18 05:52:18
@article{04b71253-57d7-4014-aaa7-2f8448ed8bc5,
  abstract     = {{<p>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. </p>}},
  author       = {{Gram, Magnus and Ekström, Claes and Holmqvist, Bo and Carey, Galen and Wang, Xiaoyang and Vallius, Suvi and Hellström, William and Ortenlöf, Niklas and Agyemang, Alex Adusei and Smith, Lois E.H. and Hellström, Ann and Mangili, Alexandra and Barton, Norman and Ley, David}},
  issn         = {{0378-5866}},
  keywords     = {{Brain development; Insulin-like growth factor-1 system; Intraventricular hemorrhage; Prematurity; Vascular development}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{5}},
  pages        = {{281--295}},
  publisher    = {{Karger}},
  series       = {{Developmental Neuroscience}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1159/000516665}},
  doi          = {{10.1159/000516665}},
  volume       = {{43}},
  year         = {{2021}},
}