In situ hybridization studies of mRNA encoding the major 70 kDa heat shock/stress protein, hsp7O, have demonstrated its prolonged expression in vulnerable hippocampal CAl neurons after transient global ischemia. These cells also experience a lasting impairment of protein synthesis that may contribute to such a superinduction phenomenon. The proto-oncogene, c-fos, shows only transiently increased expression but with a distribution identical to that of hsp7O mRNA at early recirculation intervals. These results suggest that related signal transduction mechanisms may be responsible for the induction of these RNAs, and support the utility of hsp7O hybridization as a possible indicator of some aspect of persistent neuronal activation. A threshold of 2 minutes ischemia has been established for induction of hsp7O in the gerbil. A more complex pattern of induction is observed after hyperthermia, with a predominantly glial and vascular distribution of immunoreactive protein but a superimposed neuronal localization of hsp7O MRNA during increasingly severe hyperthermia. The major direction of future studies is to utilize changes in hsp7O, c-fos and other mRNAs and proteins as tools for identifying the precise contributions of individual cell types to the evolution of pathophysiology following diverse brain insults, and to elucidate the specific signal transduction mechanisms involved.
