Neuroprotection of adenoviral-vector-mediated GDNF expression against kainic-acid-induced excitotoxicity in the rat hippocampus

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for several types of neurons. In the present study, we examined the protective roles of adenoviral-vector-delivered GDNF (Ad-GDNF) in the hippocampus damaged by kainic-acid (KA)-induced excitotoxicity using GAD-67 immunoreactivity, immunoblot analysis, behavioral test, 5-bromo-2-deoxyuridine (BrdU) and TUNEL assay. Ad-GDNF was pre-inoculated into the KA-treated rat hippocampus 7 days before KA injection. Ad-GDNF resulted in the suppression of KA-induced tonic-clonic convulsions. In situ apoptosis assay demonstrated a significant reduction in apoptotic cells in the CA3 and dentate hilus regions of the Ad-GDNF-pre-inoculated rats (Ad-GDNF-KA), compared to the KA rats. Striking reductions in the density of GAD-67 neurons were also observed in the CA3 and dentate hilus regions of the KA rats. On the other hand, the number of GAD-67-positive cells was recovered to the control levels in the Ad-GDNF-KA rats. Immunoblot analysis further confirmed that GAD-67 and Bcl-2 expression increased in the Ad-GDNF-KA rats compared to KA rats. Taken together, these results suggest that Ad-GDNF may serve to control KA-induced hippocampal cell loss and behavioral seizure.