Perinatal Brain Injury

Perinatal brain injury related to hypoxic-ischemic encephalopathy or extreme prematurity results in neurologic and mental handicaps.

Brain injury develops over an extended period after HI and neuroprotective cooling post-insult has proven effective in asphyxiated newborns.

However, cooling only saves one out of seven exposed to severe asphyxia and is not safe in developing countries or in preterm infants.

In order to develop improved protective strategies, we need a better molecular understanding of the pathophysiology and explore complementary therapeutic approaches. Our hypothesis is that mitochondria have a key role for evolution of secondary brain injury.

We will study: A. the importance of mitochondrial fragmentation and mitophagy in neonatal models of injury; B.  the neuroprotective effect of the glucagon-like peptide 1 receptor agonist Exenatide in a pre-clinical piglet model of hypoxic-ischemic encephalopathy and explore its mechanism of action; C. the neuroprotective mechanism of human mesenchymal stem cells; D. biomarkers of asphyxia for improved fetal monitoring and to assist in the selection of infants for neuroprotective therapy.

Increased understanding of mechanisms of brain injury may result in development of novel neuroprotective strategies in newborns.

Both Exenatide and mesenchymal stem cells have potential for clinical implementation as neuroprotectants in the neonatal setting and may reduce neurological handicaps in children and adults.