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

Claes Ekström, Niklas Ortenlöf, Amanda Kristiansson, Bo Holmqvist, Åsa Jungner, Suvi Vallius, Xiaoyang Wang, Ann Hellström, Norman W. Barton, Galen Carey, David Ley, Magnus Gram

Research output: Contribution to journalArticlepeer-review

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 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.
Original languageEnglish
Article number19847
Pages (from-to)1-12
JournalScientific Reports
Volume13
DOIs
Publication statusPublished - 2023

Subject classification (UKÄ)

  • Anesthesiology and Intensive Care

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