The aim of this study was to explore whether brain-derived neurotrophic factor (BDNF) can improve neuronal survival in cell cultures of rat dentate gyrus subjected to a hypoglycaemic insult. Glucose deprivation for 15 h caused severe neuronal loss (about 70%). BDNF added either 24 h before or 4 h after onset of hypoglycaemia completely protected granule cells against this insult-induced damage. Nerve growth factor (NGF) had similar effects. These findings support the hypothesis that the rapid upregulation of BDNF mRNA in dentate granule cells after brief periods of hypoglycaemic coma and other insults is a local protective mechanism.