Preischemic blood glucose supply to the brain modulates HSP(72) synthesis and neuronal damage in gerbils.
Preischemic hyperglycemia is known to aggravate brain damage caused by transient forebrain ischemia. Because heat shock proteins (HSPs) 72 have been proposed to play a protective role against ischemic neuronal injury, we studied the HSP(72) mRNA expression and protein synthesis in gerbils subjected to 10 min bilateral carotid occlusion under normoglycemic, hyperglycemic and fasting conditions. HSP(72) mRNA expression and HSP(72) synthesis were studied using in situ hybridization and immunostaining, respectively. After 8 h of blood recirculation, HSP(72) mRNAs were expressed in all the hippocampal subfields of the three different groups, with higher expression in the hyperglycemic gerbils. After 48 h of reperfusion, HSP(72) 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 gerbils exhibited intense HSP(72) immunoreactivity in the CA(1), whereas an absence of immunoreactivity was observed in that area in the other groups. Finally, ischemia was also associated with marked astrocytic activation, as evidenced by GFAP immunostaining. Overall results indicate that preischemic differences in blood glucose supply to the brain are related to HSP(72) mRNA expression (in terms of duration) and to HSP(72) protein induction (in terms of intensity) in the vulnerable CA(1) neurons of the hippocampus. Ability of CA(1) neurons to synthesize HSP(72) proteins was associated with higher neuronal survival in the fasted group after 48 h of reflow, suggesting a protective role of HSP(72), even though evaluation of neuronal damage at 7 days indicated that neuronal death was mainly delayed in the time.
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, 7 bld Jeanne d'Arc, 21033, Dijon Cedex, France.
P
P
Garnier
N
N
Bertrand
B
B
Flamand
A
A
Beley
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007773:Lactates / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007773:Lactates