Brain Endothelial Research	Laboratory of Molecular Neurobiology Brain Endothelial Research
	Members Current Research Publications

MODEL SYSTEM
Due to its complex functions the BBB plays an important role in the clinical practice. First, there is increasing evidence that the BBB is involved  in the pathomechanism of a large number of CNS diseases like stroke, brain trauma and tumors, neurodegenerative disorders. Second, due to the relative impermeability of the barrier, many drugs are unable to reach the CNS in therapeutically relevant concentration, making the BBB as one of the major impediments in the treatment of CNS disorders. In order to be able to directly investigate molecular mechanisms regulating BBB function we are using an in vitro model based on the culture of cerebral endothelial cells. The model can be used for:
basic research
applied research for the study of the interaction of drugs with the BBB and transport of different drugs through the BBB.
Our methods of investigation include Western-blot, phosphorylation analysis, proteomics, real-time PCR, RNA silencing, zymography, immunofluorescence etc.

SIGNALING IN BRAIN ENDOTHELIAL CELLS UNDER PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS
The permeability of the BBB is under complex control. This control is mediated by a large number of signaling molecules many of them being localized to the junctional complex. Our research is focused on the signal transduction pathways in cerebral endothelial cells activated by pathological conditions like oxidative stress, hyperosmosis or presence of inflammatory mediators. Recently we were able to identify src kinase and the receptor tyrosin kinase Axl as key elements of endothelial signaling.

INTERACTION OF METASTATIC TUMOR CELLS WITH THE BBB
Brain metastases are clinically diagnosed in the majority of patients having secondary localizations of melanoma. The prognosis for these patients is very poor and treatment can be difficult because of rapid progression of the disease. Since the brain does not have lymphatic vessels, melanoma cells have to transmigrate through the blood-brain barrier in order to reach the brain parenchyma. During this process the tumor cells either must disrupt intercellular junctions or use the transcellular route. We have shown that a disintegration of the junctional complex could play an important role in the formation of brain metastases in malignant melanoma.