Studying astrogliosis during brain development in preterm infants with intraventricular haemorrhage.
by Andriana Gialeli (PI Prof. Dr. Axel Heep)

Preterm infants, born at under 32 weeks gestation, are at high risk of suffering from brain injury due to intraventricular haemorrhage (IVH) which causes the accumulation of cerebrospinal fluid (CSF). CSF, that is been produced by choroid plexus and runs along the lateral ventricle walls, provides factors which support the division, development, and migration of the surrounding neural stem/progenitor cells (NSPCs). Alterations in CSF composition (growth factors, hormones, miRNAs) after a brain injury can cause the deregulation of NSPCs homeostasis and contribute to central nervous system implications. While there are many studies about adult NSPCs-CSF interaction after an intraventricular haemorrhage (IVH) in adults, less is known about this interaction during development.  The aims of this PhD project are to:

1. Explore the potential interactions between signalling molecules, such as miRNAs, in the CSF of preterm infants with neural progenitor cells (NPCs) in the pre-term developing brain after IVH. 
2. Develop an in vitro model of IVH using human induced pluripotent stem cells (iPSCs) derived choroid plexus organoids which have been shown to be able to produce artificial CSF.
3. Investigate if/how this artificial CSF and choroid plexus are being affected by this IVH-like insult

Molecular characterization of neonatal hypoxic - ischaemic brain injury in a rat model.
by Christina Schäfer (PI Prof. Dr. Axel Heep)

Hypoxic-ischaemic encephalopathy (HIE), which is caused by an interruption in the blood and oxygen supply to the brain, is one of the most common causes of cerebral damage during the perinatal period. HIE occurs in about 1.5 - 2.5 per 1000 newborns and despite existing treatment options, such as hypothermia, it is associated with a high mortality rate. Surviving infants also remain at high risk of developing permanent neurological disorders, including cerebral palsy (CP) and epilepsy.

The interruption of oxygen supply can be attributed to a variety of causes, such as an umbilical cord prolapse or placental abruption. The lack of oxygen disturbs the energy metabolism in nerve cells and activates various intracellular signalling pathways. As a result, necrotic cell death and apoptosis are initiated in cells. In this context, the hippocampus, cortex, striatum and thalamus could be identified as the most severely damaged brain regions in both the foetal human brain and the Rice-Vannucci animal model.

Due to the fact that the exact molecular mechanisms that lead to HIE in newborns are still largely unexplored, further research is needed here, also with regard to the development of suitable therapeutic approaches. The aryl hydrocarbon receptor (AhR), which is already expressed in the brain during early embryonic development and is involved in many physiological as well as pathophysiological cell processes, could possibly represent a key regulator in the development of HIE in newborns.

The aims of this PhD project are to:

1. investigate the aryl hydrocarbon receptor (AhR)-signalling pathway which is robustly expressed during early brain development thereby serving as a potential target for modulation of brain injury.

2. address the question why HIE affects brains in male babies more severely than in female babies.

3. assess the influence of a perinatal HI event on the inherent aging process of the brain studying so-called epigenetic clock genes.

Methods: DNA/RNA isolation, DNA methylation, RT-PCR and other molecular biological and protein biochemical techniques.

→ This project is performed in collaboration with PD Dr. Hemmen Sabir (Department of Neonatology, University of Bonn) 
https://www.neonatologie-bonn.de/experimentelle-neonatologie/
 

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