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- Ekström, Claes, et al.
(författare)
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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
- 2019
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Konferensbidrag (refereegranskat)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 severemorbidity. 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.
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