Our research group focuses on how adverse early life events (such as perinatal asphyxia and preterm birth) compromise brain development and we aim to develop therapeutic strategies. Since the brain is the body’s highest energy consumer and the neonatal brain undergoes the most rapid pace of growth in the first 1000 days of life, early life nutrition is crucial for healthy brain development. Therefore, we study the effects of milk-derived nutritional components on brain development and the potential to use early life nutraceuticals to improve neurodevelopmental outcome after neonatal brain injury.

Investigating Human Milk Oligosaccharides for Neuroprotection in Preterm Infants

IIn particular, we investigate the neuroprotective effects of human milk components for preterm infants, with a specific focus on human milk oligosaccharides (HMOs). HMOs are the third most component of human milk and play an important role in infant health by supporting gut microbiota and immune system development. By taking a bench-to-bedside approach, we study the potential association between HMOs intake and neurodevelopment in preterm infants and in animal models for preterm brain injury. We investigate whether and how HMOs supplementation can reduce preterm brain injury.

Exploring DHA as a Building Block for Neonatal Brain Repair and Regeneration

Another important component of human milk, omega-3 fatty acid docosahexaenoic acid (DHA) is an important building block for the brain. DHA serves an important role in axonal outgrowth and synaptogenesis of neurons, particularly during the first 1000 days of life. Therefore, we investigate the therapeutic effects of DHA supplementation on neonatal brain injury, as sole therapy, and also in combination with regenerative therapies with the aim to provide building blocks to repair the injured brain. We translate these finding to the neonate in the Dolphin CONTINUE randomized controlled trial, where we assess the effects of this diet on brain development and long-term outcome in preterm infants.

Image: A DHA-supplemented diet increased n-3 fatty acids in the brain. Specifically in males, the experimental diet reduced lesion size and neuroinflammation. The experimental diet also improved novel object recognition, but no significant effects on motor performance were observed. Current data indicates that early life DHA supplementation may provide neuroprotection after perinatal HI.

Exploring the Therapeutic Potential of Milk-Derived Extracellular Vesicles for Preterm Brain Injury

Milk contains not only nutritional building blocks but also bioactive components that actively regulate the development of newborns. Among these are cell-derived extracellular vesicles (EVs), which serve as vehicles for cell-cell communication. Milk EVs show promise for therapeutic applications due to their anti-inflammatory and regenerative properties.

In this project, we aim to unravel the effects of milk EVs on the injured preterm brain. We investigate the in vitro functional effects of milk EVs on neural cell types using multi-omics techniques. In vivo, we focus on the migratory capacity of milk EVs to the brain and the therapeutic efficacy of intranasal milk EV administration on preterm brain injury. In the clinical setting, we explore the feasibility of intranasal administration of EV-containing milk plasma to preterm infants with brain injury (post-hemorrhagic ventricular dilatation), and assess effects on neuroinflammatory and neuroregenerative markers in cerebrospinal fluid. The goal is to develop a protocol for a first-in-human trial to evaluate the efficacy of intranasal milk EV therapy for preterm brain injury.