Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR.
IUGR in humans is associated with impaired pre- and postnatal neurodevelopment, and subsequent postnatal cognition, resulting in lower IQ, poorer memory, visuomotor and executive function skills, as well as behavioural and attentional problems. Experimental models of IUGR are needed to allow direct testing of causality and interventions, and have benefits in reducing both confounding by comorbidities such as prematurity, and variation due to environment and genetics. This review describes and discusses experimental models of IUGR in which neurodevelopmental and cognitive outcomes of IUGR have been reported. We consider the timing of neurodevelopment relative to birth and to the period of restriction, as well as the effects of each experimental perturbation on the fetal environment and development, before discussing neurodevelopmental and cognitive outcomes for progeny as fetuses, neonates and into adolescent and adult life. Experimental IUGR induces broadly similar outcomes to human IUGR, with altered brain morphology, in particular grey matter loss and discordant trajectory of white matter development, and poorer cognition and memory reported in various studies. Nevertheless, there remain gaps in knowledge of neurodevelopment in experimental models. We end the review with recommendations for the design of future studies to further investigate the mechanisms underlying adverse neurodevelopmental consequences of IUGR, and to evaluate interventions that may subsequently improve outcomes of IUGR in humans.
Robinson Research Institute, University of Adelaide, South Australia, Australia; Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, South Australia, Australia; School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Damien S
DS
Hunter
School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Susan J
SJ
Hazel
Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Animal and Veterinary Sciences, University of Adelaide, South Australia, Australia.
Karen L
KL
Kind
Robinson Research Institute, University of Adelaide, South Australia, Australia; Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, South Australia, Australia.
Julie A
JA
Owens
Robinson Research Institute, University of Adelaide, South Australia, Australia; Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, South Australia, Australia.
Julia B
JB
Pitcher
Robinson Research Institute, University of Adelaide, South Australia, Australia; Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, South Australia, Australia. Electronic address: kathy.gatford@adelaide.edu.au.
Kathryn L
KL
Gatford
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans
Animal models; Brain; Cognition; IUGR; Neurodevelopment