18 - The effects of intrauterine inflammation and mechanical ventilation on brain injury in preterm fetal sheep.
Monday, May 1, 2023
9:30 AM – 11:30 AM ET
Poster Number: 18 Publication Number: 18.434
Graeme Polglase, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; Nhi T. Tran, The Hudson Institute of Medical Research, Melbourne, Victoria, Australia; Ainsley Somers, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; kayla Kockaya, The Ritchie Centre, The Hudson Institute of Medical Research, Melbourne, Victoria, Australia; Zahrah Azman, The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Beth J. Allison, Hudson Institute of Medical Research, Northcote, Victoria, Australia; Kyra YY. Chan, The Ritchie Centre and Monash University, Singapore, N/A, Singapore; Robert Galinsky, Hudson Institute of Medical Research, MELBOURNE, Victoria, Australia
Associate DIrector Hudson Institute of Medical Research Melbourne, Victoria, Australia
Background: Preterm infants often require ventilatory support at birth which can inadvertently cause ventilation-induced brain injury. Given that intrauterine infection (chorioamnionitis) is a major cause of preterm birth, understanding the interaction and effect mechanical ventilation and intrauterine inflammation have on the preterm brain is critical. In order to isolate the effects of ventilation and/or chorioamnionitis from other confounders (e.g. haemodynamic and oxidative stress pathways) on preterm brain injury, we developed an in-utero ventilation model in preterm fetal sheep. Objective: To investigate the effects of intrauterine inflammation and mechanical ventilation on white matter and grey matter inflammation and injury in fetal sheep. We hypothesised that ventilation-induced brain inflammation and injury would be exacerbated by prior exposure to intrauterine inflammation. Design/Methods: Chronically instrumented preterm fetal sheep (115 ± 3 days of gestation) were randomly allocated to 4 groups: unventilated control + saline (UVC, n=9), in utero ventilation + saline (IUV, n=8), unventilated control + LPS (UVC+LPS, n=7), or in utero ventilation + LPS (IUV+LPS, n=7). Fetuses received a single intratracheal dose of 1 mg LPS or saline 1 hour prior to the initiation of IUV or no ventilation. After 24 h, fetal brains were collected and paraffin-embedded for immunohistochemical analysis and mRNA assessment using Fluidigm. Results: LPS exposure increased numbers of IBA-1+ microglia in the subcortical white matter (SCWM), putamen and cortex, with increased numbers of microglia showing an ameboid morphology (P< 0.05 vs UVC). IUV increased numbers of Olig-2+ oligodendrocytes within the internal capsule (P< 0.05 vs UVC). Neither LPS or IUV affected numbers of TUNEL+ cells (apoptosis) or GFAP+ astrocytes compared to UVC. The combination of IUV and LPS did not alter any histological markers induced by IUV and LPS independently. LPS increased mRNA levels of IL1B, TNF, CD44, CASP3 (P< 0.05 vs UVC and IUV). LPS and IUV increased cyclooxygenase 2 expression in the sub-cortical white matter (P< 0.05 vs all).
Conclusion(s): Intrauterine inflammation increased histological and mRNA markers of brain inflammation and injury. Twenty for hours of mechanical ventilation after exposure to intrauterine inflammation had limited effects on histological and mRNA markers of white and grey matter inflammation and injury.
