Gene Expression and the Response to Ischemic Insults in Brain

Studies in a Gerbil Model of Induced Tolerance

Abstract

Brief ischemic insults protect against injury following subsequent longer and otherwise damaging periods of ischemia, although such protective effects have usually been quite variable. Selective changes in gene expression are considered good candidates for mediators of the tolerance phenomenon, and the stress protein, hsp72, has received considerable attention in this regard. In recent experiments we have monitored the interval of ischemic depolarization following brief periods of occlusion and have identified depolarization thresholds for tolerance, for injury and for various changes in gene expression. While hsp72 is clearly inducible after moderate insults that do not injure neurons, our results indicate that neuronal protection can be achieved by even milder insults that do not appreciably induce hsp72, but that do induce immediate-early genes of the Fos and Jun families with lower depolarization thresholds. In addition, these studies provide the basis for a reproducible model in which mechanisms of tolerance can be further studied.