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Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

Artikel i vetenskaplig tidskrift
Författare K. Sveinsdottir
J. K. Lansberg
S. Sveinsdottir
M. Garwicz
L. Ohlsson
Ann Hellström
L. Smith
M. Gram
D. Ley
Publicerad i Developmental Neuroscience
Volym 39
Nummer/häfte 6
Sidor 487-497
ISSN 0378-5866
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor 487-497
Språk en
Länkar doi.org/10.1159/000480428
Ämnesord Preterm birth, Cerebellum, Insulin-like growth factor 1, Purkinje cells, Sonic hedgehog protein, factor-i, sonic-hedgehog, active caspase-3, bergmann glia, brain, expression, infants, birth, proliferation, proteins
Ämneskategorier Neurovetenskaper

Sammanfattning

Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar prolif-eration, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r(2) = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a welldefined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population. (C) 2017 S. Karger AG, Basel

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