Adenovirus-mediated gene transfer of glial cell line-derived neurotrophic factor prevents ischemic brain injury after transient middle cerebral artery occlusion in rats

To examine a possible protective effect of exogenous glial cell line-derive d neurotrophic factor (GDNF) gene expression against ischemic brain injury, a replication-defective adenoviral vector containing GDNF gene (Ad- GDNF) was directly injected into the cerebral cortex at 1 day before 90 minutes o f transient middle cerebral artery occlusion (MCAO) in rats. 2,3,5-Tripheny ltetrazolium chloride staining showed that infarct volume of the Ad-GDNF-in jected group at 24 hours after the transient MCAO was significantly smaller than that of vehicle- or Ad-LacZ-treated group. Enzyme-linked immunosorben t assay (ELISA) for immunoreactive GDNF demonstrated that GDNF gene product s in the Ad-GDNF-injected group were higher than those of vehicle-treated g roup at 24 hours after transient MCAO. Immunoreactive GDNF staining was obv iously detected in the cortex around the needle track just before or 14 hou rs after MCAO in the Ad-GDNF group, whereas no or slight GDNF staining was detected in the vehicle group. The numbers of TUNEL, immunoreactive caspase -3, and cytochrome c-positive neurons induced in the ipsilateral cerebral c ortex at 24 hours after transient MCAO were markedly reduced by the Ad-GDNF group. These results suggest that the successful exogenous GDNF gene trans fer ameliorates ischemic brain injury after transient MCAO in association w ith the reduction of apoptotic signals.