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Evaluation of recombinant human IGF‑1/IGFBP‑3 on intraventricular hemorrhage prevention and survival in the preterm rabbit pup model

Ekström, Claes LU orcid ; Ortenlöf, Niklas LU ; Kristiansson, Amanda LU ; Holmqvist, Bo ; Jungner, Åsa LU ; Vallius, Suvi LU ; Wang, Xiaoyang ; Hellström, Ann ; Barton, Norman W. and Carey, Galen , et al. (2023) In Scientific Reports 13. p.1-12
Abstract
Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes
of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility
of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral
blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal
time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/
rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of
rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH
was evaluated... (More)
Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes
of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility
of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral
blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal
time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/
rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of
rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH
was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part
of the study, the highest incidence of IVH (> 60%), occurred when glycerol was administered at the
earliest timepoint, e.g., 6 h after birth. At later time-points (18 and 24 h) the incidence decreased
substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals.
To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth,
as reported in human interventional studies, additional studies are needed to further characterize and
establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival
in the preterm rabbit pup. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
article number
19847
pages
1 - 12
publisher
Nature Publishing Group
external identifiers
  • pmid:37963901
  • scopus:85176401894
ISSN
2045-2322
DOI
10.1038/s41598-023-46611-0
language
English
LU publication?
yes
id
c8037fea-16ab-4c6f-b7ea-7b0df0cc9499
date added to LUP
2023-12-01 09:22:56
date last changed
2023-12-02 04:06:40
@article{c8037fea-16ab-4c6f-b7ea-7b0df0cc9499,
  abstract     = {{Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes<br/>of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility<br/>of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral<br/>blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal<br/>time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/<br/>rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of<br/>rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH<br/>was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part<br/>of the study, the highest incidence of IVH (&gt; 60%), occurred when glycerol was administered at the<br/>earliest timepoint, e.g., 6 h after birth. At later time-points (18 and 24 h) the incidence decreased<br/>substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals.<br/>To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth,<br/>as reported in human interventional studies, additional studies are needed to further characterize and<br/>establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival<br/>in the preterm rabbit pup.}},
  author       = {{Ekström, Claes and Ortenlöf, Niklas and Kristiansson, Amanda and Holmqvist, Bo and Jungner, Åsa and Vallius, Suvi and Wang, Xiaoyang and Hellström, Ann and Barton, Norman W. and Carey, Galen and Ley, David and Gram, Magnus}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  pages        = {{1--12}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Evaluation of recombinant human IGF‑1/IGFBP‑3 on intraventricular hemorrhage prevention and survival in the preterm rabbit pup model}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-46611-0}},
  doi          = {{10.1038/s41598-023-46611-0}},
  volume       = {{13}},
  year         = {{2023}},
}