Project Details
Projekt
What is wrong with the vasculature in bronchopulmonary dysplasia?
Subject Area
Pneumology, Thoracic Surgery
Anatomy and Physiology
Nuclear Medicine, Radiotherapy, Radiobiology
Anatomy and Physiology
Nuclear Medicine, Radiotherapy, Radiobiology
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 420759458
Bronchopulmonary dysplasia (BPD) is a severe disease affecting immaturely born newborns. BPD is associated with aberrant lung development and pulmonary Hypertension (PH). Although it is known that BPD affects the pulmonary vasculature which is critical for pathogenesis and later PH development, the changes are still unclear both qualitatively and quantitatively. The current Project aims at closing this gap by an innovative combination of newly developed methods of quantification and 3D reconstruction of the vasculature. Besides normal postnatal development, the lungs of three different BPD models will be investigated: hyperoxic mouse, preterm/hyperoxic rabbit and preterm baboon. The preterm baboon model is very close to human BPD whereas the mouse and rabbit are important for future testing of therapeutic approaches. Lungs will be fixed by vascular perfusion and processed for stereological quantification or 3D reconstruction. The latter will be performed using µCT data sets with subsequent light microscopic Analysis of the arterial tree or by using electron microscopic 3D data sets of the capillary network of whole alveoli (Serial block-face scanning electron microscopy). Due to the novel methodology we will be able to address various questions that were previously impossible to be answered. For example we will be able to assign morphological changes to specific branches of the vessel tree which is only possible by the combined µCT and microscopy approach. Another example are the alterations of the alveolar capillary Network. With a new stereological method (Euler-Poincaré characteristic) we will be able to estimate the number of capillaries in the alveolar septa which helps to identify the nature of the aberrant vascular development and to relate it to the delayed process of alveolarization. Answering These and other questions specified in the proposal are essential to better understand BPD pathogenesis and develop new therapeutic strategies.
DFG Programme
Research Grants
