Postischemic temperature as a modulator of the stress response in brain: dissociation of heat shock protein 72 induction from ischemic tolerance after bilateral carotid artery occlusion in the gerbil.

Brief ischemia induces tolerance to subsequent more severe insults, and induction of the 70 kDa heat shock/stress protein, hsp72, has been suggested to play a role. This study tested the requirement for hsp72 expression in a gerbil tolerance model in which postischemic temperature was varied to modulate the level of hsp72 induction. Gerbils were subjected to 2 min bilateral common carotid artery occlusion and kept under halothane anesthesia for 90 min, during which rectal temperature was either maintained at 37 degrees C (normothermic, NT) or elevated to 39.5 degrees C (hyperthermic, HT) during 15-60 min recirculation. Hsp72 mRNA expression was determined by in situ hybridization with a (35)S-labeled oligonucleotide probe at 3, 24 and 48 h. Separate groups were subjected to a test challenge of 5 min ischemia 48 h after the priming insult, and CA1 neuron counts were obtained at 1 week. Significant protection was observed in both NT and HT groups. However, while 90% of hippocampi from NT animals showed detectable protection of CA1 neurons, less than half showed detectable hsp72 mRNA induction. These results indicate that, within the limits of experimental detection, hsp72 expression is not required for induction of ischemic tolerance.