Gene expression and induced ischemic tolerance following brief insults

Abstract

Striking changes in gene expression occur after transient ischemic insults, including the induction of heat shock proteins that are believed to play a central role in cellular defense mechanisms, and proto-oncogene (immediate-early gene) transcription factors that regulate the expression of diverse target genes. Such effects potentially contribute to a wide range of pathophysiological responses. A number of studies have characterized models of induced ischemic tolerance in which brief priming insults are demonstrated to result in reduced vulnerability to subsequent challenges. In the present study we have optimized a model of induced ischemic tolerance in the gerbil by carefully monitoring the duration of ischemic depolarization during each insult. Using this model we demonstrate that the threshold depolarization required to induce tolerance is comparable to those for induction of several transcription factor mRNAs, while mRNA encoding the heat shock protein, hsp72, is strongly induced only after more severe insults that approach the threshold for ischemic neuronal injury.