Characterization of the role of NF-kB in cerebral ischemia and sepsis

The ubiquitous transcription factor NF-kB is an important mediator of the inflammatory response and a regulator of apoptosis. In an animal model of focal cerebral ischemia, we were able to show that NF-kB is activated in the brain and enlarges the infarct. The cells in which the functionally relevant activation of NF-kB occurs during cerebral ischemia will now be clarified by transgenically expressing an NF-kB inhibitor in various brain cells. In the next step, we want to characterize the signaling cascade leading to NF-kB activation in vitro in these cells. Inhibitors of NF-kB activation will then be tested in vivo for their effectiveness in focal cerebral ischemia. In a second part, we want to examine whether NF-kB is activated in the brain during sepsis. The significance of this activation for the symptoms of sepsis will be investigated by transgenically expressing an NF-kB inhibitor in various brain cells. This will clarify the role of NF-kB in the pathogenesis of cerebral ischemia and sepsis.