The heat shock/stress response in focal cerebral ischemia

Focal ischemia results in striking changes in gene expression. Induction of hsp72, a member of the family of 70 kDa heat shock/stress proteins is a widely studied component of the generalized cellular response to injury known as the 'stress response' that is detected in brain after ischemia and other insults. This overview summarizes observations on hsp72 expression in models of focal cerebral ischemia, considering its cellular distribution, factors affecting its transcriptional and translational expression, and its potential relevance to post-ischemic pathophysiology. Hsp72 expression is essentially limited to regions in which cerebral blood flow falls below 50% of control levels, provided that residual perfusion allows synthesis of the induced mRNA and protein. The cellular distribution of hsp72 depends on the nature of the ischemic insult, with preferential vascular expression in severely ischemic territory that is destined to necrose, pronounced neuronal expression throughout the ischemic 'penumbra', and limited glial involvement in a narrow zone immediately surrounding the infarct. Together with results in other injury models, these observations indicate that hsp72 induction identifies discrete populations of surviving cells that are metabolically compromised, but not irreversibly damaged after focal ischemia. Available evidence suggests that the stress response is an important component of cellular defense mechanisms, and that successful accumulation of hsp72 is critical to survival following ischemia. Its expression may also contribute to mechanisms of induced ischemic tolerance. Future studies may be expected to more fully characterize the range of altered gene expression in response to focal ischemic injury and to establish specific roles for hsp72 and other induced proteins in the progression of injury and recovery following such insults.