Localization of 70 kDa stress protein mRNA induction in gerbil brain after ischemia

Induction of mRNA encoding the 70 kDa stress/heat shock protein, hsp70, was evaluated in post-ischemic gerbil brain by in situ hybridization using an oligonucleotide probe selective for stress-inducible members of this gene family. Expression of hsp70 sequences was most pronounced in hippocampal CA1 neurons that fail to accumulate immunoreactive hsp70 protein, and that are selectively lost following ischemia. Hybridizable RNA continued to be expressed in CA1 through at least 48 h, essentially until the onset of cell death in this model. In contrast, dentate granule cells and CA2 neurons destined to survive the insult showed transient induction of hsp70 mRNA during the first 24 h of recirculation that disappeared prior to the detection of maximal hsp70 immunoreactivity in these cell populations. Pretreatment with a single injection of MK-801 (10 mg/kg) considerably attenuated the induction of hsp70 mRNA in hippocampus at 6 h of recirculation, an effect apparently mediated by persistent drug-induced hypothermia. The drug did not prevent the later, selective appearance of hsp70 hybridization in CA1 neurons at 24 h, nor did it protect against the subsequent loss of these cells. These results demonstrate a prolonged postischemic stress response at the transcriptional level in vulnerable hippocampal neurons, and suggest its utility as a marker for neuronal pathophysiology associated with mechanisms mediating delayed neuronal death.