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

TITLE=Mechanical ventilation induces brainstem inflammation in preterm fetal sheep

JOURNAL=Frontiers in Pediatrics

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1225294

DOI=10.3389/fped.2023.1225294

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>Preterm 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.</p></sec><sec><title>Methods</title><p>Preterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation <italic>in utero</italic>. At 112<bold> ±</bold> 1 d gestation, fetuses received either mechanical ventilation (VENT; <italic>n</italic> = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; <italic>n</italic> = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.</p></sec><sec><title>Results</title><p><italic>In utero</italic> 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 (<italic>p</italic> &lt; 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (<italic>p</italic> = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (<italic>p</italic> = 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.</p></sec><sec><title>Conclusion</title><p>Mechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.</p></sec>