Therapeutic time window of adenovirus-mediated GDNF gene transfer after transient middle cerebral artery occlusion in rat

Abstract

The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad–GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad–GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad–LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.