Molecular characterisation 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 of 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 approximately 1.5 - 2.5 out of 1000 newborns and is associated with a high mortality rate despite existing treatment options, such as hypothermia. Surviving infants are also at high risk of developing permanent neurological disorders, including cerebral palsy (CP) and epilepsy.

The interruption of the oxygen supply can be due to a variety of causes, such as umbilical cord prolapse or placental abruption. The lack of oxygen disrupts 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 were 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 required 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 and pathophysiological cell processes, could possibly represent a key regulator in the development of HIE in newborns.

The aims of this PhD project are:

1. To analyse the aryl-hydrocarbon receptor (AhR) signalling pathway.

2. To investigate why male infants experience more severe brain damage after HIE compared to female infants.

3. Evaluation of the influence of a perinatal HI event on the inherent aging process of the brain by investigating so-called epigenetic "clock genes".

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

→ This project is carried out in collaboration with PD Dr Hemmen Sabir (Head of Experimental Neonatology, University of Bonn):

https://www.neonatologie-bonn.de/experimentelle-neonatologie

Influence of odours on early human development

During pregnancy, an embryo or foetus in the uterus is constantly exposed to various olfactory stimuli, both from the foetus itself and from the mother, which can be influenced, for example, by the mother's choice of food and other factors. The sense of smell is the only human sense that has a direct connection to the hippocampus and the limbic system. Both areas are ontogenetically among the oldest areas of the brain and are associated with the processing of emotions, memories and feelings. Although the olfactory system is not yet fully developed even in mature newborns and continues to develop beyond birth, children can already perceive odours in the womb and even recognise them after birth. Whether and how these perceptions influence the child's development is largely unknown. Newborns react extremely sensitively and in a differentiated way to maternal odours (e.g. breast milk) and it is assumed that these odours play a role both in the establishment of oral feeding and in the development of the mother-child bond. Especially as the sense of taste is closely linked to the sense of smell.

If a premature birth occurs, this development takes place abruptly and prematurely under altered conditions. The close physical contact with the mother immediately after birth, also known as bonding, is interrupted and natural olfactory experiences are limited and may be almost completely prevented by the use of respiratory support measures. In addition, premature babies are exposed to new, potentially unpleasant and therefore stress-inducing odours (disinfectants etc.). How the changed olfactory environment and exposure to olfactory stress affect early childhood development will be investigated at the end of projects carried out by the Perinatal Neurobiology Working Group.

The following aspects will be considered:

• How does the odour environment altered by premature birth affect the development and functionality of the olfactory system? (Investigation of the expression and methylation of various genes of the olfactory system).
• What effect does olfactory stress have on premature babies? (Measurement of different odourants with an electronic nose).
• What role do different natural odorants play in early childhood development?
• What effects does olfactory stimulation have on premature babies? Whether and how can this be used in clinical practice?

If you are interested, please contact

[email protected] & [email protected]

Please contact Christina Sobirey for student projects and research opportunities:

[email protected]