The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs

Vanesa Stojanovska, Samantha K. Barton, Mary Tolcos, Andrew W. Gill, Martin Kluckow, Suzanne L. Miller, Valerie Zahra, Stuart B. Hooper, Robert Galinsky, Graeme R. Polglase

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVC Sal , n = 4; UVC BM, n = 6) were humanely killed without intervention; ventilated lambs (Vent Sal , n = 5; Vent BM , n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVC BM than in UVC Sal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in-Vent BM lambs (p < 0.05 vs. Vent Sal ). In the subcortical WM, microglial infiltration was increased in the Vent Sal group compared to UVC Sal . The proportion of activated microglia and protein extravasation was higher in the Vent BM group compared to Vent Sal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the Vent BM group compared to UVC Sal, UVC BM , and Vent Sal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

Original languageEnglish
Number of pages11
JournalDevelopmental Neuroscience
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Keywords

  • Betamethasone
  • Brain injury
  • Cerebral haemorrhage
  • Mechanical ventilation
  • Preterm birth
  • White matter

Cite this

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title = "The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs",
abstract = "Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVC Sal , n = 4; UVC BM, n = 6) were humanely killed without intervention; ventilated lambs (Vent Sal , n = 5; Vent BM , n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVC BM than in UVC Sal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in-Vent BM lambs (p < 0.05 vs. Vent Sal ). In the subcortical WM, microglial infiltration was increased in the Vent Sal group compared to UVC Sal . The proportion of activated microglia and protein extravasation was higher in the Vent BM group compared to Vent Sal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the Vent BM group compared to UVC Sal, UVC BM , and Vent Sal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.",
keywords = "Betamethasone, Brain injury, Cerebral haemorrhage, Mechanical ventilation, Preterm birth, White matter",
author = "Vanesa Stojanovska and Barton, {Samantha K.} and Mary Tolcos and Gill, {Andrew W.} and Martin Kluckow and Miller, {Suzanne L.} and Valerie Zahra and Hooper, {Stuart B.} and Robert Galinsky and Polglase, {Graeme R.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1159/000496466",
language = "English",
journal = "Developmental Neuroscience",
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The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs. / Stojanovska, Vanesa; Barton, Samantha K.; Tolcos, Mary; Gill, Andrew W.; Kluckow, Martin; Miller, Suzanne L.; Zahra, Valerie; Hooper, Stuart B.; Galinsky, Robert; Polglase, Graeme R.

In: Developmental Neuroscience, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs

AU - Stojanovska, Vanesa

AU - Barton, Samantha K.

AU - Tolcos, Mary

AU - Gill, Andrew W.

AU - Kluckow, Martin

AU - Miller, Suzanne L.

AU - Zahra, Valerie

AU - Hooper, Stuart B.

AU - Galinsky, Robert

AU - Polglase, Graeme R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVC Sal , n = 4; UVC BM, n = 6) were humanely killed without intervention; ventilated lambs (Vent Sal , n = 5; Vent BM , n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVC BM than in UVC Sal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in-Vent BM lambs (p < 0.05 vs. Vent Sal ). In the subcortical WM, microglial infiltration was increased in the Vent Sal group compared to UVC Sal . The proportion of activated microglia and protein extravasation was higher in the Vent BM group compared to Vent Sal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the Vent BM group compared to UVC Sal, UVC BM , and Vent Sal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

AB - Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVC Sal , n = 4; UVC BM, n = 6) were humanely killed without intervention; ventilated lambs (Vent Sal , n = 5; Vent BM , n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVC BM than in UVC Sal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in-Vent BM lambs (p < 0.05 vs. Vent Sal ). In the subcortical WM, microglial infiltration was increased in the Vent Sal group compared to UVC Sal . The proportion of activated microglia and protein extravasation was higher in the Vent BM group compared to Vent Sal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the Vent BM group compared to UVC Sal, UVC BM , and Vent Sal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

KW - Betamethasone

KW - Brain injury

KW - Cerebral haemorrhage

KW - Mechanical ventilation

KW - Preterm birth

KW - White matter

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U2 - 10.1159/000496466

DO - 10.1159/000496466

M3 - Article

JO - Developmental Neuroscience

JF - Developmental Neuroscience

SN - 0378-5866

ER -