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THE INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) SYSTEM IN THE PRETERM RABBIT PUP : A CHARACTERIZATION OF THE IGF-1 MRNA EXPRESSION IN LIVER, IGF-1 PROTEIN LEVELS IN SERUM AND BRAIN DISTRIBUTION OF IGF-1 RECEPTORS

Ekström, Claes LU orcid ; Holmqvist, Bo ; Gram, Magnus LU orcid and Ley, David LU (2019) the 3rd Congress of joint European Neonatal Societies (jENS)
Abstract
IGF-1 is an essential regulator of fetal growth and brain development. Preterm birth in the human is followed by a rapid decrease in serum levels of IGF-1 and decreased levels of IGF-1 have been associated with development of severe
morbidity. A recent clinical trial indicated that supplementation with IGF-1 prevented development of severe intraventricular hemorrhage (IVH) in extremely preterm infants. In order to better understand possible mechanisms involved in IGF-1-induced IVH prevention, we evaluated important aspects of the endogenous IGF-1 system; IGF-I mRNA expression in the liver and associated serum protein levels and brain IGF-1 receptor (IGFR) distribution in the preterm rabbit.

Rabbit pups were delivered by... (More)
IGF-1 is an essential regulator of fetal growth and brain development. Preterm birth in the human is followed by a rapid decrease in serum levels of IGF-1 and decreased levels of IGF-1 have been associated with development of severe
morbidity. A recent clinical trial indicated that supplementation with IGF-1 prevented development of severe intraventricular hemorrhage (IVH) in extremely preterm infants. In order to better understand possible mechanisms involved in IGF-1-induced IVH prevention, we evaluated important aspects of the endogenous IGF-1 system; IGF-I mRNA expression in the liver and associated serum protein levels and brain IGF-1 receptor (IGFR) distribution in the preterm rabbit.

Rabbit pups were delivered by cesarean section at E29 (preterm) or by vaginal delivery (term = E32), housed in a controlled environment and fed twice daily with bovine colostrum via a gastric tube. Serum concentrations of IGF-1protein and liver expression of IGF-1 mRNA were determined at 0, 2, 6, 12, 24, 48 and 72 h of age in preterm pups. Paraffin brain sections from perfusion fixed untreated animals (preterm pups at 20 h and term pups at 5-7 h and 96 h) were prepared for immunohistochemistry against IGF1R, by labeling with primary antibodies against IGF1R, and processed for chromogen visualization and density/quantitation analysis with confocal microscopy.

Mean (SD) serum concentrations of IGF-1 decreased from 166 (33) ng/ml at birth (E29) to 28 (9) ng/ml at day 3 (P0). Hepatic expression of IGF-1 mRNA did not vary over time. The IGF1R was widely distributed in multiple brain regions in both preterm and term pups (Fig). The most abundant density of IGF1R was observed in the choroid plexus, the subfornical organ, the meninges, major fiber tracts, the cortex and sub-ependymal germinal zones. The IGF1R, was mainly localized on outer cell membranes, on cell bodies and along nerve fibers. Quantitative analysis of IGF1R immunoreactivity showed similar IGF1R densities in preterm and term pups of corresponding ages. IGF1R density decreased with increasing postnatal age in term pups.

In line with what is observed in the preterm human infant, serum protein levels of IGF-1 in the preterm rabbit pup decrease rapidly following birth. The IGF1R is widely expressed in the brain following birth, with high expressions in regions and structures relevant for vessel rupture in IVH. The preterm rabbit thus presents a well-suited model for characterization and evaluation of mechanisms involved in IGF-1 induced prevention of IVH. (Less)
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organization
publishing date
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Contribution to conference
publication status
published
subject
editor
Carey, Galen ; Wang, Xiaoyang ; Hellström, Ann and Barton, Norman W.
conference name
the 3rd Congress of joint European Neonatal Societies (jENS)
conference location
Maastricht, Netherlands
conference dates
2019-09-17 - 2019-09-21
language
English
LU publication?
yes
id
1b78b245-e0f7-458d-b863-4e4b33d9a410
date added to LUP
2019-09-25 10:50:49
date last changed
2021-04-29 02:35:43
@misc{1b78b245-e0f7-458d-b863-4e4b33d9a410,
  abstract     = {{IGF-1 is an essential regulator of fetal growth and brain development. Preterm birth in the human is followed by a rapid decrease in serum levels of IGF-1 and decreased levels of IGF-1 have been associated with development of severe<br/>morbidity. A recent clinical trial indicated that supplementation with IGF-1 prevented development of severe intraventricular hemorrhage (IVH) in extremely preterm infants. In order to better understand possible mechanisms involved in IGF-1-induced IVH prevention, we evaluated important aspects of the endogenous IGF-1 system; IGF-I mRNA expression in the liver and associated serum protein levels and brain IGF-1 receptor (IGFR) distribution in the preterm rabbit.<br/><br/>Rabbit pups were delivered by cesarean section at E29 (preterm) or by vaginal delivery (term = E32), housed in a controlled environment and fed twice daily with bovine colostrum via a gastric tube. Serum concentrations of IGF-1protein and liver expression of IGF-1 mRNA were determined at 0, 2, 6, 12, 24, 48 and 72 h of age in preterm pups. Paraffin brain sections from perfusion fixed untreated animals (preterm pups at 20 h and term pups at 5-7 h and 96 h) were prepared for immunohistochemistry against IGF1R, by labeling with primary antibodies against IGF1R, and processed for chromogen visualization and density/quantitation analysis with confocal microscopy. <br/><br/>Mean (SD) serum concentrations of IGF-1 decreased from 166 (33) ng/ml at birth (E29) to 28 (9) ng/ml at day 3 (P0). Hepatic expression of IGF-1 mRNA did not vary over time. The IGF1R was widely distributed in multiple brain regions in both preterm and term pups (Fig). The most abundant density of IGF1R was observed in the choroid plexus, the subfornical organ, the meninges, major fiber tracts, the cortex and sub-ependymal germinal zones. The IGF1R, was mainly localized on outer cell membranes, on cell bodies and along nerve fibers. Quantitative analysis of IGF1R immunoreactivity showed similar IGF1R densities in preterm and term pups of corresponding ages. IGF1R density decreased with increasing postnatal age in term pups.<br/><br/>In line with what is observed in the preterm human infant, serum protein levels of IGF-1 in the preterm rabbit pup decrease rapidly following birth. The IGF1R is widely expressed in the brain following birth, with high expressions in regions and structures relevant for vessel rupture in IVH. The preterm rabbit thus presents a well-suited model for characterization and evaluation of mechanisms involved in IGF-1 induced prevention of IVH.}},
  author       = {{Ekström, Claes and Holmqvist, Bo and Gram, Magnus and Ley, David}},
  editor       = {{Carey, Galen and Wang, Xiaoyang and Hellström, Ann and Barton, Norman W.}},
  language     = {{eng}},
  month        = {{09}},
  title        = {{THE INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) SYSTEM IN THE PRETERM RABBIT PUP : A CHARACTERIZATION OF THE IGF-1 MRNA EXPRESSION IN LIVER, IGF-1 PROTEIN LEVELS IN SERUM AND BRAIN DISTRIBUTION OF IGF-1 RECEPTORS}},
  year         = {{2019}},
}