A Translational Model of Incomplete Catch‐Up Growth: Early‐Life Hypoxia and the Effect of Physical Activity

Abstract

Advances in therapies have led to prolonged survival from many previously lethal health threats in children, notably among prematurely born babies and those with congenital heart disease. Evidence for catch‐up growth is common in these children, but in many cases the adult phenotype is never achieved. A translational animal model is required in which specific tissues can be studied over a reasonable time interval. We investigated the impact of postnatal hypoxia (HY) (12%O2 (HY12) or 10% O2 (HY10)) on growth in rats relative to animals raised in room air. Subgroups had access to running wheels following the HY period. Growth was fully compensated in adult HY12 rats but not HY10 rats. The results of this study indicate that neonatal hypoxia can be a useful model for the elucidation of mechanisms that mediate successful catch‐up growth following neonatal insults and identify the critical factors that prevent successful catch‐up growth.

Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish

“…Another critical aspect of hypoxia is the effect on the developmental process occurring during reoxygenation periods after hypoxia, for example, how neurons execute a compensatory accelerated "catch-up process" after returning to normoxia (i.e., reoxygenation) following hypoxia. This catchup response (i.e., hypoxia-recovery, HR) has been reported to coordinate embryonic/fetal growth and developmental rate in response to changing environmental conditions, including oxygen levels (Azzam and Mortola, 2007;Kamei et al, 2011;Radom-Aizik et al, 2018). Although the "catch-up" response has been found as an evolutionarily conserved mechanism ranging from Caenorhabditis elegans to mammalian systems, the precise mechanism of the "catch-up" response in the developing brain is poorly understood (Hales and Ozanne, 2003;Ozanne and Hales, 2004;Saenger et al, 2007).…”