Neuroprotection in newborn infants at risk for neuro-developmental impairment

The project focuses on development and implementation of novel neuro-protective strategies aiming to promote brain development in newborns at high risk for neuro-developmental impairment.

Our previous work has provided the basis for intervention in very preterm infants with substitution of the complex IGF-I/IGFBP-3 aiming to support pathways essential for brain development.

Clinical implementation in randomized study shows a reduction in major morbidities and has led to new research questions evaluated in pre-clinical models.

Cerebral intraventricular hemorrhage (IVH) is an acquired brain lesion in preterm infants with severe implications for neuro-development.

In a rabbit pup model of IVH, extracellular hemoglobin, released and metabolized following hemorrhage, is a potent inducer of pathways leading to inflammation and apoptosis.

Scavenging of cell-free hemoglobin is evaluated in small and large animal models and appears a promising means of neuro-protection.Newborns with congenital heart disease are at risk for brain damage and neuro-developmental impairment.

Surgery assisted by cardio-pulmonary bypass exposes the brain to hyperoxemia and hemolysis with increased systemic levels of extracellular hemoglobin.

Hyperoxemia and extracellular hemoglobin may act synergistically causing blood-brain barrier damage and a white matter brain inflammation.

These relationships are explored in newborn infants and causal mechanisms and intervention are evaluated in a novel animal model.