21 Postischemic Stress Response in Brain

Abstract

I. INTRODUCTION
Cerebral ischemia occurs in the context either of focal reductions in blood flow to brain regions (stroke) or as a global deficit after cardiac arrest. In the United States alone, these conditions annually affect 500,000 and more than 1 million individuals, respectively (Wolf et al. 1992). As summarized below, studies in animal models have identified a prominent heat shock/stress response in the brain following such insults. It can be inferred that ischemic injury constitutes one of the primary settings in which the stress response impacts human brain pathophysiology. Parallel studies have documented a postischemic stress response in other tissues including, for example, recent studies in liver (Tacchini et al. 1993) and kidney (Van Why et al. 1992). Substantial work in cardiac ischemia is considered elsewhere in this volume (Benjamin and Williams).

In view of the anatomical complexity of the brain, the distribution of the stress response after ischemia and other insults is a particularly important issue. Most work has relied on immunocytochemistry and in situ hybridization to map the expression of a highly inducible member of the 70-kD heat shock protein family, hsp72, as an index of the stress response in the brain. Studies of other members of this family, as well as of ubiquitin and other heat shock responsive genes, are also beginning to emerge. As detailed below, striking differences in the distribution and cell-type specificity of pathology observed after global and focal ischemia are well correlated with the pattern of hsp72 expression after these insults, confirming...