Effects of intrauterine inflammation on cortical gray matter of near-term lambs

Vanesa Stojanovska, Anzari Atik, Ilias Nitsos, Béatrice Skiöld, Samantha K. Barton, Valerie A. Zahra, Karyn Rodgers, Stuart B. Hooper, Graeme R. Polglase, Robert Galinsky

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 (INJSAL N = 6, INJLPS N = 5) or a protective ventilation strategy (PROTSAL N = 5, PROTLPS N = 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.

Original languageEnglish
Article number145
JournalFrontiers in Pediatrics
Volume6
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Chorioamnionitis
  • Gray matter
  • Intrauterine inflammation
  • Neuronal loss
  • Ventilation

Cite this

Stojanovska, Vanesa ; Atik, Anzari ; Nitsos, Ilias ; Skiöld, Béatrice ; Barton, Samantha K. ; Zahra, Valerie A. ; Rodgers, Karyn ; Hooper, Stuart B. ; Polglase, Graeme R. ; Galinsky, Robert. / Effects of intrauterine inflammation on cortical gray matter of near-term lambs. In: Frontiers in Pediatrics. 2018 ; Vol. 6.
@article{9592ca029fe44e4c8c163ac7920c3bd8,
title = "Effects of intrauterine inflammation on cortical gray matter of near-term lambs",
abstract = "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 (INJSAL N = 6, INJLPS N = 5) or a protective ventilation strategy (PROTSAL N = 5, PROTLPS N = 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.",
keywords = "Chorioamnionitis, Gray matter, Intrauterine inflammation, Neuronal loss, Ventilation",
author = "Vanesa Stojanovska and Anzari Atik and Ilias Nitsos and B{\'e}atrice Ski{\"o}ld and Barton, {Samantha K.} and Zahra, {Valerie A.} and Karyn Rodgers and Hooper, {Stuart B.} and Polglase, {Graeme R.} and Robert Galinsky",
year = "2018",
month = "1",
day = "1",
doi = "10.3389/fped.2018.00145",
language = "English",
volume = "6",
journal = "Frontiers in Pediatrics",
issn = "2296-2360",
publisher = "Frontiers Media",

}

Effects of intrauterine inflammation on cortical gray matter of near-term lambs. / Stojanovska, Vanesa; Atik, Anzari; Nitsos, Ilias; Skiöld, Béatrice; Barton, Samantha K.; Zahra, Valerie A.; Rodgers, Karyn; Hooper, Stuart B.; Polglase, Graeme R.; Galinsky, Robert.

In: Frontiers in Pediatrics, Vol. 6, 145, 01.01.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of intrauterine inflammation on cortical gray matter of near-term lambs

AU - Stojanovska, Vanesa

AU - Atik, Anzari

AU - Nitsos, Ilias

AU - Skiöld, Béatrice

AU - Barton, Samantha K.

AU - Zahra, Valerie A.

AU - Rodgers, Karyn

AU - Hooper, Stuart B.

AU - Polglase, Graeme R.

AU - Galinsky, Robert

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 (INJSAL N = 6, INJLPS N = 5) or a protective ventilation strategy (PROTSAL N = 5, PROTLPS N = 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.

AB - 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 (INJSAL N = 6, INJLPS N = 5) or a protective ventilation strategy (PROTSAL N = 5, PROTLPS N = 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.

KW - Chorioamnionitis

KW - Gray matter

KW - Intrauterine inflammation

KW - Neuronal loss

KW - Ventilation

UR - http://www.scopus.com/inward/record.url?scp=85049658465&partnerID=8YFLogxK

U2 - 10.3389/fped.2018.00145

DO - 10.3389/fped.2018.00145

M3 - Article

VL - 6

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

SN - 2296-2360

M1 - 145

ER -