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Effects of Umbilical Cord Occlusion in Late Gestation on the Ovine Fetal Brain and Retina

Department of Anatomy and Cell Biology, University of Melbourne, Parkville; Department of Physiology, Monash University, Clayton, Australia; j.duncan{at}unimelb.edu.au

Emily Camm, PhD

Michelle Loeliger, BSc

Megan L. Cock, PhD

Richard Harding, DSc

Sandra M. Rees, PhD

Department of Anatomy and Cell Biology, University of Melbourne, Parkville; Department of Physiology, Monash University, Clayton, Australia

Objective: Previous studies on the effects of umbilical cord occlusion (UCO) on the fetal brain have focused on short-term alterations, and in most cases have used only subjective techniques to evaluate brain injury. Our aim was to assess quantitatively the persistent consequences of UCO on the developing brain; we also examined the retina.

Methods: We subjected fetal sheep to a single episode of UCO at 126 days of gestation (term 147 days) to induce at least 10 minutes of isoelectric fetal electrocorticogram (ECoG).

Results: UCO resulted in fetal asphyxia and transient mild alterations in fetal mean arterial pressure (MAP). UCO did not result in significant injury to the developing brain or retina when assessed 15 days after the insult. There was no change in the endogenous expression of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, nor was there a significant loss of CA1 hippocampal pyramidal cells. However, this insult did result in subtle neuropathologic alterations in the brain, including a reduction in the weight of the cerebral hemispheres, an increase in the areal density of cerebellar Purkinje cells, and enlarged perivascular spaces around blood vessels and inflammatory cells in the cerebral white matter. UCO did not affect the thickness of the central or peripheral retina or the numbers of retinal dopaminergic, cholinergic, and nitrergic amacrine cells.

Conclusions: Thus, while 10 minutes of UCO did not result in overt injury to the fetal brain or retina, the observed changes in the fetal brain suggest altered growth of neural processes, which may contribute to neurologic deficits postnatally or to increased vulnerability of the brain to later insults during either the remainder of gestation or after birth.

Key Words: Umbilical cord occlusion • fetal sheep • brain

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