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Does growth restriction increase the vulnerability to acute ventilation-induced brain injury in newborn lambs? Implications for future health and disease

Part of: DOHaD ANZ Conference 2016

Published online by Cambridge University Press:  09 August 2017

B. J. Allison ,
S. B. Hooper ,
E. Coia ,
G. Jenkin ,
A. Malhotra ,
V. Zahra ,
A. Sehgal ,
M. Kluckow ,
A. W. Gill  and
T. Yawno
...Show all authors
B. J. Allison*
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
S. B. Hooper
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
E. Coia
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
G. Jenkin
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
A. Malhotra
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Pediatrics, Monash Newborn, Monash Medical Centre, Monash University, Melbourne, VIC, Australia
V. Zahra
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
A. Sehgal
Affiliation:
Department of Pediatrics, Monash Newborn, Monash Medical Centre, Monash University, Melbourne, VIC, Australia
M. Kluckow
Affiliation:
Department of Neonatology, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
A. W. Gill
Affiliation:
Centre for Neonatal Research and Education, The University of Western Australia, WA, Australia
T. Yawno
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
G. R. Polglase
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
M. Castillo-Melendez
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
S. L. Miller
Affiliation:
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia Department of Obstetrics and Gynecology, Monash University, Clayton, VIC, Australia
*
*Address for correspondence: B. Allison, PhD, The Ritchie Centre, Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, VIC 3168, Australia. (Email: beth.allison@hudson.org.au)
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Abstract

Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood–brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.

Keywords

brain injuryFGRIUGRmechanical ventilation
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 5: Themed Issue: Australian Perspectives: Outcomes from the 2016 ANZ , October 2017 , pp. 556 - 565
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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