Initial studies demonstrated the induction of the major stress (heat shock) protein, hsp70, after transient ischemia. Induction of RNAs encoding ubiquitin has also been shown. Immunocytochemical localization of hsp70, largely in hippocampal circuitry, suggests that hsp70 may provide a marker for neuronal pathways mediating proposed excitotoxic mechanisms of neuronal damage after ischemia. Recent results have demonstrated that the ion channel antagonist MK-801 blocks hsp70 induction although it fails to protect hippocampal CA1 neurons which die after transient ischemia. This provides the basis for further pharmacological studies of physiological mechanisms responsible for such local changes in gene expression after ischemia. While postischemic hsp70 induction is neuronal, hyperthermia in vivo results in a largely glial heat shock response. In vitro studies with rat cerebellar astrocytes and granule cell neurons in culture also show selective hsp70 induction in glia and such cultures may prove useful in identifying the molecular basis of the selective glial heat shock response in vivo.
