Mechanical ventilation induces brainstem inflammation in preterm fetal sheep

Area of Science:

• Neonatal Physiology
• Neuroscience
• Respiratory Medicine

Background:

• Preterm infants often require mechanical ventilation due to immature respiratory drive.
• Prolonged mechanical ventilation can lead to systemic inflammation and ventilation-induced brain injury.
• The specific impact of mechanical ventilation on brainstem respiratory centers in preterm neonates remains largely unknown.

Purpose of the Study:

• To investigate the effects of 24-hour mechanical ventilation on inflammation and injury within the brainstem respiratory centers of preterm fetal sheep.
• To assess markers of inflammation and cellular injury in specific brainstem nuclei.

Main Methods:

• Preterm fetal sheep (110 ± 1 days gestation) underwent instrumentation for in utero mechanical ventilation.
• Fetuses received either 24 hours of mechanical ventilation (VENT, n=7) or served as controls (CONT, n=6).
• Brainstems were collected post-mortem for assessment of mRNA and histological markers of inflammation and injury.

Main Results:

• Mechanical ventilation significantly increased systemic IL-6 and IL-8 concentrations compared to controls.
• Increased numbers of ameboid microglia were observed in the nucleus tractus solitarius and raphe nucleus of ventilated fetuses.
• No significant differences in GFAP staining, caspase-3, TUNEL-positive cells, or gene expression for inflammation and injury markers were found between groups in key respiratory centers.

Conclusions:

• Mechanical ventilation in preterm fetal sheep induces a systemic inflammatory response.
• The inflammatory effects on the brainstem respiratory centers were moderate, with increased microglial activation but no significant markers of cell death or widespread injury.
• Further research is needed to fully understand the long-term consequences of ventilation on developing brainstem respiratory control.