Time Course and Cellular Distribution of Hsp27 and Hsp72 Stress Protein Expression in a Quantitative Gerbil Model of Ischemic Injury and Tolerance: Thresholds for Hsp72 Induction and Hilar Lesioning in the Context of Ischemic Preconditioning

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Abstract
The distribution and time course of expression of the heat shock/stress proteins, hsp27 and hsp72, were evaluated in a highly controlled gerbil model of ischemic injury and tolerance induction, in which the duration of ischemic depolarization in each hippocampus provides a precise quantitative index of insult severity. Gerbils were subjected to brief priming insults (2- to 3.5-minute depolarization) that produce optimal preconditioning, to severe test insults (6- to 8.5-minute depolarization) that produce complete CA1 neuron loss in naive animals, or to combined insults administered 1 week apart, after which almost complete tolerance to CA1 neuron injury is observed. Immunoreactivities of hsp27, hsp72, glial fibrillary acidic protein and microtubule-associated protein 2 (MAP2) were evaluated in animals perfused at defined intervals after the final insult in each treatment group, using a variation of established antigen-retrieval procedures that significantly improves detection of many proteins in vibratome brain sections. Hsp72 was detected in CA1 neurons of some hippocampi 2 to 4 days after preconditioning, but this was only seen after the longest priming depolarizations, whereas shorter insults that still induced optimal tolerance failed to induce hsp72. Hsp72 was induced after test insults in preconditioned hippocampi, but at a higher depolarization threshold than observed for naive animals. An astrocytic localization of hsp27 was observed in regions of neuron injury, as indicated by reduced MAP2 immunoreactivity, and was primarily restricted to dentate hilus after preconditioning insults. These results establish that limited hilar lesions are characteristic of optimal preconditioning, whereas prior neuronal expression of either hsp72 or hsp27 is not required for ischemic tolerance.

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