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Open AccessArticle

Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone

1
School of Human Sciences, University of Western Australia, Perth 6009, Australia
2
Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia
3
Centre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth 6009, Australia
4
School of Biomedical Sciences, University of Western Australia, Perth 6009, Australia
5
Developmental Imaging, Murdoch Children’s Research Institute, Melbourne 3052, Australia
6
Department of Medicine, Monash University, Melbourne 3800, Australia
7
School of Agriculture and Environment, University of Western Australia, Perth 6009, Australia
8
Murdoch Children’s Research Institute, Melbourne 3052, Australia
9
Department of Paediatrics, University of Melbourne, Melbourne 3052, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Brain Sci. 2020, 10(4), 211; https://doi.org/10.3390/brainsci10040211
Received: 3 March 2020 / Revised: 26 March 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days’ (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, n = 9), low-dose tapered dexamethasone (cumulative dose = 0.75 mg/kg, n = 8), or high-dose tapered dexamethasone (cumulative dose = 2.67 mg/kg, n = 8), for seven days. Naïve fetal lambs (136 d gestation) were used as end-point maturation controls. The left-brain hemispheres were immersion-fixed in 10 % formalin (24 h), followed by paraformaldehyde (>6 months). Image sequences were empirically optimized for T1- and T2-weighted MRI and analysed using accessible methods. Spontaneous lesions detected in the white matter of the frontal cortex, temporo-parietal cortex, occipital lobe, and deep to the parahippocampal gyrus were confirmed with histology. Neither postnatal dexamethasone treatment nor gestation showed any associations with lesion incidence, frontal cortex (total, white, or grey matter) or hippocampal volume (all p > 0.05). Postnatal dexamethasone did not appear to adversely affect neurodevelopment. Our post-mortem MRI analysis pipeline is suitable for other animal models of brain development. View Full-Text
Keywords: animals; neonatal; neurodevelopmental disorders; infant; premature; magnetic resonance imaging; neuropathology; neurology; glucocorticoids; dexamethasone animals; neonatal; neurodevelopmental disorders; infant; premature; magnetic resonance imaging; neuropathology; neurology; glucocorticoids; dexamethasone
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Yates, N.J.; Feindel, K.W.; Mehnert, A.; Beare, R.; Quick, S.; Blache, D.; Pillow, J.J.; Hunt, R.W. Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone . Brain Sci. 2020, 10, 211.

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