Protection Against Ischemic Brain Damage By GDNF Affecting Cell Survival And Death Signals

Neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) on cell survival and death signals were investigated after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Immunoreactivities of phosphorylated Akt (p-Akt),cleaved caspase-9 (c-cas9),and-3 (c-cas3) increased after the reperfusion in the penumbra in vehicle group with peaks at 3 h,8 h,and 1 d,respectively. Topical application of GDNF (6. 8ug/9u1) on brain surface potentiated and prolonged p-Akt activation,but suppressed activation of the caspases,and reduced the number of terminal deoxynucleotidyl transferase-mediated dIJDP-biotin in situ nick labeling (TUNEL) positive cells. These results suggest that GDNF plays a protective effect against ischemic injury by controlling the balance between Akt pathway and caspase cascades.