ABSTRACT
In the ischemic penumbra, progressive cellular injury during acute focal brain ischemia is extremely multifactorial. The many individual mediators that have been demonstrated to have a pathologic role in experimental stroke models seem to act as a constellation of minor causes for ongoing damage such that no single mediator accounts for a major share of the ultimate tissue injury (Hallenbeck and Frerichs, 1993). It is very difficult to design an effective approach to problems that arise from the aggregate activity of multiple minor causes. For this reason, we have been interested in the regulation of natural and induced states of ischemic tolerance in animal models as having the potential to guide efforts to develop effective stroke therapy. Analysis of the critical intracellular signaling that regulates adaptive responses to various forms of stress and confers cellular tolerance to ischemia could provide valuable clues to new therapeutic strategies.
