INVESTIGATION OF BLOOD-BRAIN BARRIER CHANGES IN ACUTE PANCREATITIS: A CELL CULTURE AND CLINICAL STUDY
Fruzsina R. Walter1, Szilvia Veszelka1, Ana R. Santa-Maria1, Judit P. Vigh1, András Harazin1, Petra Pallagi3, József Maléth3, Zsolt Balla2, Péter Hegyi4, 5, Zoltan Rakonczay2, Maria A. Deli1
Acute pancreatitis (AP) is a serious inflammatory disease of the pancreas, which in severe cases can lead to systemic inflammation and organ failure. Since the central nervous system is affected in 10% of all severe AP cases manifesting in pancreatic encephalopathy, it is crucial to understand the mechanism of its development. Earlier research from our laboratory showed blood-brain barrier (BBB) permeability elevation in the rat non-invasive acute pancreatitis model induced by the administration of l-ornithine. In the current study we aimed to explore these BBB integrity compromising mechanisms, using a rat primary brain endothelial cell co-culture model in static conditions and under dynamic settings using our biochip model (Walter et al., 2016). We found, that l-ornithine treatment decreased cell impedance and elevated permeability after 24 h treatment. Key interendothelial junctional and adhesion molecule expression and morphology was compromised. ROS production was increased and mitochondrial network was also damaged while no intracellular Ca2+ or mitochondrial membrane potential alteration occurred. To test BBB integrity changes during AP, serum from clinical patients of mild, moderate and severe AP was collected and levels of BBB leakage markers S100-calcium-binding-protein-B and neuron specific enolase was tested using ELISA kits. The effect of sera on barrier integrity was also investigated on a human brain endothelial cell line model (hCMEC/D3). Our results may help to better understand the background of BBB alterations during AP and could lead to the development of future treatment strategies. Grant support: János Bolyai Research Fellowship of the HAS, OTKA PD-128480 and UNKP-19-4-SZTE-42.