Impact of the EphB/ephrinB system on inflammation and edema formation during cerebral ischemia

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Stroke is one of the most relevant causes of death in the western world and responsible for 6 billion euro economic costs caused by illness in Germany annually. As the pathophysiological and regenerative mechanisms of this disease are only partially understood, no causative therapy dealing with the consequences of the ischemic insult is available. In this context, the role of the Eph/ephrin-receptor/ligand-system has not been investigated so far although it decisively controls genesis, architecture and function of the brain. Our preliminary work on a mouse stroke model indicates that the membrane-associated ligands ephrinB1 and ephrinB2 as well as the receptors EphB2 and EphB4 are crucial for the pro-inflammatory activation and navigation of endothelial and immune cells in the context of post-ischemic processes in the brain. Thus, this proposal is ought to investigate as to how the EphB/ephrinB-system regulates the function of endothelial and immune cells under these circumstances. Consequently, the working program is specifically focused on the analysis of (i) the relevance of ephrinB1/B2 for the function of the blood-brain-barrier with respect to the formation of brain edema as well as the transmigration of leukocytes (monocytes, granulocytes) and (ii) the ischemia-related activation of leukocytes and resident immune cells (microglia, astroglia) by the EphB/ephrinB-system.