Preischemic blood glucose supply to the brain modulates HSP72 synthesis and neuronal damage in gerbils

Preischemic hyperglycemia is known to aggravate brain damage caused by tran sient forebrain ischemia. Because heat shock proteins (HSPs) 72 have been p roposed to play a protective role against ischemic neuronal injury, we stud ied the HSP72 mRNA expression and protein synthesis in gerbils subjected to 10 min bilateral carotid occlusion under normoglycemic, hyperglycemic and fasting conditions. HSP72 mRNA expression and HSP72 synthesis were studied using in situ hybridization and immunostaining, respectively. After 8 h of blood recirculation, HSP72 mRNAs were expressed in all the hippocampal subf ields of the three different groups, with higher expression in the hypergly cemic gerbils. After 48 h of reperfusion, HSP72 mRNAs had almost completely disappeared in the hyper- and normoglycemic groups, and were more strongly expressed in the CA(1) neurons of the fasted group. At this time, fasted g erbils exhibited intense HSP72 immunoreactivity in the CA(1), whereas an ab sence of immunoreactivity was observed in that area in the other groups. Fi nally, ischemia was also associated with marked astrocytic activation, as e videnced by GFAP immunostaining. Overall results indicate that preischemic differences in blood glucose supply to the brain are related to HSP72 mRNA expression (in terms of duration) and to HSP72 protein induction (in terms of intensity) in the vulnerable CA(1) neurons of the hippocampus. Ability o f CA(1) neurons to synthesize HSP72 proteins was associated with higher neu ronal survival in the fasted group after 48 h of reflow, suggesting a prote ctive role of HSP72, even though evaluation of neuronal damage at 7 days in dicated that neuronal death was mainly delayed in the time. (C) 1999 Elsevi er Science B.V. All rights reserved.