AMELIORATION OF HYPOXIC AND HYPOGLYCEMIC DAMAGE TO CEREBRAL ENDOTHELIAL-CELLS - EFFECTS OF HEAT-SHOCK PRETREATMENT

Induction of the 70 kDa heat shock protein (HSP70) by hypoxia and/or h ypoglycemia and the effects of prior heat shock on injury owing to hyp oxia and/or hypoglycemia were studied in rat cerebral endothelial cell s. Hypoxia and/or hypoglycemia treatment resulted in increased express ion of HSP70 only when such treatment was sufficient to cause detectab le injury and when the initial treatment was followed by exposure of t he cells to 24 h of normoxia and normoglycemia. Heat shock induced 24 h prior to treatment with 48 h of hypoxia slightly reduced endothelial cell damage as measured by fraction of lactate dehydrogenase release (10% decrease in injury). There was a more dramatic effect of prior he at shock on the moderate damage produced by 12 h of combined hypoxia a nd hypoglycemia (45% decrease), whereas the severe damage produced by 24 h of hypoxia and hypoglycemia was decreased by prior heat shock by only 16%. These results indicate that the hypoxia and hypoglycemia occ urring in conjunction with ischemia are more likely to result in heat shock protein expression when there is injury to the tissue. Furthermo re, heat shock protects cerebral endothelial cells from hypoxia and hy poglycemia either by slowing the initial development of injury or by d elaying the onset of injury.