THE HEAT-SHOCK STRESS-RESPONSE AFTER BRAIN-LESIONS - INDUCTION OF 72 KDA HEAT-SHOCK-PROTEIN (CELL-TYPES INVOLVED, AXONAL-TRANSPORT, TRANSCRIPTIONAL REGULATION) AND PROTEIN-SYNTHESIS INHIBITION

The cerebral stress response is examined following a variety of pathol ogical conditions such as focal and global ischemia, administration of excitotoxins, and hyperthermia. Expression of 72 kDa heat shock prote in (Hsp70) and hsp70 mRNA, the mechanism underlying induction of hsp70 mRNA involving activation of heat shock factor 1, and inhibition of c erebral protein synthesis are different aspects of the stress response considered here. The results are compared with those in the literatur e on induction, transcriptional regulation, expression, and cellular l ocation of Hsp70, with a view to getting more insight into the functio n of the stress response in the injured brain. The present results ill ustrate that Hsp70 can be expressed in cells affected at Various degre es following an insult that will either survive or die as the brain le sion develops, depending on the severity of cell injury. This indicate s that, under certain circumstances, synthesized Hsp70 might be necess ary but not sufficient to ensure cell survival. Other situations invol ve uncoupling between synthesis of hsp70 mRNA and protein, probably du e to very strict protein synthesis blockade, and often result in cell loss. Cells eventually will die if protein synthesis rates do not go b ack to normal after a period of protein synthesis inhibition. The stre ss response is a dynamic event that is switched on in neural cells sen sitive to a brain insult. The stress response is, however, tricky, as affected cells seem to need it, have to deal transiently with it, but eventually be able to get rid of it, in order to survive. Putative the rapeutic treatments can act either selectively, potentiating the synth esis of Hsp70 protein and recovery of protein synthesis, or preventing the stress response by deadening the insult severity. (C) 1997 Elsevi er Science Ltd.