Research: Brain development is altered in rabbit fetuses with congenital diaphragmatic hernia

Prenat Diagn

. 2023 Jan 10.

 doi: 10.1002/pd.6309. Online ahead of print.

Brain development is altered in rabbit fetuses with congenital diaphragmatic hernia

Lennart VAN DER Veeken 1 2 3Francesca Maria Russo 1 2Tom Bleeser 4 5David Basurto 1Doaa Emam 1 6Yannick Regin 1Willy Gsell 7Uwe Himmelreich 7Luc DE Catte 1 2Steffen Rex 4 5Jan Deprest 1 2 8

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Introduction: Children with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Some changes are already present prenatally. Herein, we further examined how the brain develops in fetal rabbits with surgically created DH.

Methods: Two fetuses underwent surgical DH creation on day 23 (term=d31). DH-pups and littermate controls were harvested at term. Ten DH-pups and 11 controls underwent transcardial perfusion for brain fixation and measurement of brain volume, brain folding, neuron and synaptic density, pre-oligodendrocyte count, proliferation and vascularization. Twelve other DH and 11 controls had echocardiographic assessment of cardiac output and aortic and cerebral blood flow, Magnetic Resonance Imaging (9.4T) for cerebral volumetry, and molecular assessment of vascularization markers.

Results: DH-pups had lower lung-to-body weight ratio (1.3±0.3 vs 2.4±0.3%; p<0.0001) and lower heart-to-body weight ratio (0.007±0.001 vs 0.009±0.001; p=0.0006) but comparable body weight and brain-to-body weight ratio. DH-pups had a lower left ventricular ejection fraction, aortic and cerebral blood flow (39±8 vs 54±15mm/beat; p=0.03) as compared to controls but similar left cardiac ventricular morphology. Fetal DH-brains were similar in volume but the cerebellum was less folded (perimeter/surface area: 25.5±1.5 vs 26.8±1.2; p=0.049). Furthermore, DH brains had a thinner cortex (143±9 vs 156±13µm; p=0.02). Neuron densities in the white matter were higher in DH fetuses (124±18 vs 104±14; p=0.01), with comparable proliferation rate. Pre-oligodendrocyte count was lower, coinciding with lower endothelial cell count.

Conclusion: Rabbits with DH had altered brain development compared to controls prenatally, indicating that brain development is already altered prenatally in CDH. This article is protected by copyright. All rights reserved.

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