HYPER-GLYCEMIA AND HYPERCAPNIA SUPPRESS BDNF GENE-EXPRESSION IN VULNERABLE REGIONS AFTER TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT

Preischemic hyperglycemia or superimposed hypercapnia exaggerates brai n damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of fo rebrain ischemia under normoglycemic, hyperglycemic, or hypercapnic co nditions. Compared with normoglycemic animals, the increase of BDNF mR NA in dentate granule cells was attenuated and that in CA3 pyramidal n eurons completely prevented in hyperglycemic rats. No ischemia-induced increases of BDNF mRNA levels in the hippocampal formation were detec ted in hypercapnic animals. Hyperglycemic and hypercapnic rats showed transiently decreased expression of BDNF mRNA levels in the cingulate cortex, which was not observed in normoglycemic animals. The results s uggest that suppression of the BDNF gene might contribute to the incre ased vulnerability of the CA3 region and cingulate cortex in hyperglyc emic and hypercapnic animals.