Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Bryan Richardson

Abstract

Aberrant brain development in utero accompanied by fetal growth restriction (FGR) increases the risk of neurodevelopmental disorders in later life. However there are limited non-invasive biomarkers in the brain for the early identification of said neurodevelopmental disorders in an animal model of FGR. Guinea pig sows were fed either ad libitum (Control) or 70% of the control diet pre-pregnancy, increasing to 90% at mid-pregnancy (MNR) creating appropriately grown (AGA) Control and FGR-MNR neonates, respectively. Three to four weeks corrected post-natal age, neonates were imaged using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, and were killed 48-72 hours later for histological analysis. FGR-MNR neonates had smaller brain weights, whole brain volume, hippocampal volume and lateral ventricle volume, which correlate to histological findings. While there is a reduction in the hippocampal volume, there are no differences in hippocampus metabolite ratios between the AGA-Control and FGR-MNR neonates. Interestingly, there was a reduction in the width of the stratum oriens and stratum radiatum in the hippocampus proper, as well as the width of the polymorphic layer in the dentate gyrus, with no changes in pyramidal and granule cell number in the FGR-MNR neonates compared to AGA-Control neonates. In conclusion, MNR in guinea pigs produces FGR neonates that display catch up growth and structural differences in the brains while no changes in the metabolite levels in the hippocampal region of the brain. Together these results involve MRI and MRS as reliable imaging tools to detect the presence of brain injury for the future use of biomarkers for neurodevelopmental disorders and potential therapeutic interventions.

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