Frontiers in Pediatrics (Oct 2023)

Mechanical ventilation induces brainstem inflammation in preterm fetal sheep

  • Kayla Vidinopoulos,
  • Kayla Vidinopoulos,
  • Zahrah Azman,
  • Zahrah Azman,
  • Ainsley Somers,
  • Ainsley Somers,
  • Valerie A. Zahra,
  • Alison Thiel,
  • Hui Lu,
  • Yen Pham,
  • Nhi Thao Tran,
  • Nhi Thao Tran,
  • Beth J. Allison,
  • Beth J. Allison,
  • Eric Herlenius,
  • Stuart Hooper,
  • Stuart Hooper,
  • Robert Galinsky,
  • Robert Galinsky,
  • Graeme R. Polglase,
  • Graeme R. Polglase

DOI
https://doi.org/10.3389/fped.2023.1225294
Journal volume & issue
Vol. 11

Abstract

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BackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.MethodsPreterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.ResultsIn utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.ConclusionMechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.

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