Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs

Introduction: Ventilation causes cerebral white matter inflammation and injury, which is exacerbated by intrauterine inflammation. However, the effects on cortical gray matter are not well-known. Our aim was to examine the effect of ventilation on the cerebral cortex of near-term lambs exposed to in...

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Main Authors: Vanesa Stojanovska, Anzari Atik, Ilias Nitsos, Béatrice Skiöld, Samantha K. Barton, Valerie A. Zahra, Karyn Rodgers, Stuart B. Hooper, Graeme R. Polglase, Robert Galinsky
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fped.2018.00145/full
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author Vanesa Stojanovska
Anzari Atik
Ilias Nitsos
Béatrice Skiöld
Samantha K. Barton
Samantha K. Barton
Valerie A. Zahra
Karyn Rodgers
Stuart B. Hooper
Stuart B. Hooper
Graeme R. Polglase
Graeme R. Polglase
Robert Galinsky
Robert Galinsky
author_facet Vanesa Stojanovska
Anzari Atik
Ilias Nitsos
Béatrice Skiöld
Samantha K. Barton
Samantha K. Barton
Valerie A. Zahra
Karyn Rodgers
Stuart B. Hooper
Stuart B. Hooper
Graeme R. Polglase
Graeme R. Polglase
Robert Galinsky
Robert Galinsky
author_sort Vanesa Stojanovska
collection DOAJ
description Introduction: Ventilation causes cerebral white matter inflammation and injury, which is exacerbated by intrauterine inflammation. However, the effects on cortical gray matter are not well-known. Our aim was to examine the effect of ventilation on the cerebral cortex of near-term lambs exposed to intrauterine inflammation.Method:Pregnant ewes at 119 ± 1 days gestation received an intra-amniotic injection of saline or lipopolysaccharide (LPS; 10 mg). Seven days later, lambs were randomized to either a high tidal volume injurious ventilation strategy (INJSALN = 6, INJLPSN = 5) or a protective ventilation strategy (PROTSALN = 5, PROTLPSN = 6). Respiratory parameters, heart rate and blood gases were monitored during the neonatal period. At post-mortem, the brain was collected and processed for immunohistochemical assessment. Neuronal density (NeuN), apoptotic cell death (caspase 8 and TUNEL), microglial density (Iba-1), astrocytic density (GFAP), and vascular protein extravasation (sheep serum) were assessed within the frontal, parietal, temporal and occipital lobes of the cerebral cortex.Results:A significant reduction in the number of neurons in all cortical layers except 4 was observed in LPS-exposed lambs compared to controls (layer #1: p = 0.041; layers #2 + 3: p = 0.023; layers #5 + 6: p = 0.016). LPS treatment caused a significant increase in gray matter area, indicative of edema. LPS+ventilation did not cause apoptotic cell death in the gray matter. Astrogliosis was not observed following PROT or INJ ventilation, with or without LPS exposure. LPS exposure was associated with vascular protein extravasation.Conclusion:Ventilation had little effect on gray matter inflammation and injury. Intrauterine inflammation reduced neuronal cell density, caused edema of the cortical gray matter, and blood vessel extravasation in the brain of near-term lambs.
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spelling doaj.art-ea485b859d4f434091e81eded9647a332022-12-21T19:58:15ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602018-06-01610.3389/fped.2018.00145348865Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term LambsVanesa Stojanovska0Anzari Atik1Ilias Nitsos2Béatrice Skiöld3Samantha K. Barton4Samantha K. Barton5Valerie A. Zahra6Karyn Rodgers7Stuart B. Hooper8Stuart B. Hooper9Graeme R. Polglase10Graeme R. Polglase11Robert Galinsky12Robert Galinsky13The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Women's and Children's Health, Karolinska Institute, Stockholm, SwedenThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaCentre of Clinical Brain Sciences, University of Edinburgh, Edinburgh, United KingdomThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaIntroduction: Ventilation causes cerebral white matter inflammation and injury, which is exacerbated by intrauterine inflammation. However, the effects on cortical gray matter are not well-known. Our aim was to examine the effect of ventilation on the cerebral cortex of near-term lambs exposed to intrauterine inflammation.Method:Pregnant ewes at 119 ± 1 days gestation received an intra-amniotic injection of saline or lipopolysaccharide (LPS; 10 mg). Seven days later, lambs were randomized to either a high tidal volume injurious ventilation strategy (INJSALN = 6, INJLPSN = 5) or a protective ventilation strategy (PROTSALN = 5, PROTLPSN = 6). Respiratory parameters, heart rate and blood gases were monitored during the neonatal period. At post-mortem, the brain was collected and processed for immunohistochemical assessment. Neuronal density (NeuN), apoptotic cell death (caspase 8 and TUNEL), microglial density (Iba-1), astrocytic density (GFAP), and vascular protein extravasation (sheep serum) were assessed within the frontal, parietal, temporal and occipital lobes of the cerebral cortex.Results:A significant reduction in the number of neurons in all cortical layers except 4 was observed in LPS-exposed lambs compared to controls (layer #1: p = 0.041; layers #2 + 3: p = 0.023; layers #5 + 6: p = 0.016). LPS treatment caused a significant increase in gray matter area, indicative of edema. LPS+ventilation did not cause apoptotic cell death in the gray matter. Astrogliosis was not observed following PROT or INJ ventilation, with or without LPS exposure. LPS exposure was associated with vascular protein extravasation.Conclusion:Ventilation had little effect on gray matter inflammation and injury. Intrauterine inflammation reduced neuronal cell density, caused edema of the cortical gray matter, and blood vessel extravasation in the brain of near-term lambs.https://www.frontiersin.org/article/10.3389/fped.2018.00145/fullchorioamnionitisintrauterine inflammationgray matterventilationneuronal loss
spellingShingle Vanesa Stojanovska
Anzari Atik
Ilias Nitsos
Béatrice Skiöld
Samantha K. Barton
Samantha K. Barton
Valerie A. Zahra
Karyn Rodgers
Stuart B. Hooper
Stuart B. Hooper
Graeme R. Polglase
Graeme R. Polglase
Robert Galinsky
Robert Galinsky
Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
Frontiers in Pediatrics
chorioamnionitis
intrauterine inflammation
gray matter
ventilation
neuronal loss
title Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
title_full Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
title_fullStr Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
title_full_unstemmed Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
title_short Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs
title_sort effects of intrauterine inflammation on cortical gray matter of near term lambs
topic chorioamnionitis
intrauterine inflammation
gray matter
ventilation
neuronal loss
url https://www.frontiersin.org/article/10.3389/fped.2018.00145/full
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