Introduction: Mechanical ventilation can be lifesaving for preterm infants but is associated with an increased risk of adverse neurological outcomes. We aimed to determine if administering human amnion epithelial cells (hAECs), which have anti-inflammatory and regenerative properties, to mechanically ventilated preterm lambs would affect white and grey matter inflammation and injury.
Materials and methods: Preterm lambs (0.85 of gestation) were delivered by caesarean section and mechanically ventilated for 48 hours or killed immediately after birth (unventilated control). Ventilated lambs received 3 ml surfactant (Curosurf) via an endotracheal tube, immediately prior to delivery (with or without 90x106 hAECs), and 3 ml intravenous saline (with or without 90x106 hAECs, consistent with endotracheal administration) immediately after birth. Brain tissue was collected for immunohistochemical assessment of neuroinflammation and injury.
Results: Mechanical ventilation reduced neuronal survival in the cerebral cortex and striatum (P<0.05 for ventilation groups vs. unventilated control). Ventilation reduced astrocyte survival and increased microglial activation, total numbers of (Olig-2+) oligodendrocytes, cell proliferation and blood brain barrier permeability in the intragyral and periventricular white matter (P<0.05 for ventilation groups vs. unventilated control). Administration of hAECs at birth did not reduce markers of neuroinflammation and injury within the white or grey matter in ventilated preterm lambs (NS; ventilation+saline vs. ventilation+hAECs).
Discussion: Forty-eight hours of mechanical ventilation caused neuroinflammation and injury in the grey and white matter of preterm lambs. Administration of hAECs at birth did not prevent or augment neuroinflammation and injury in ventilated preterm lambs.