Protection against ischemic brain damage by GDNF affecting cell survival and death signals

摘要

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 phospborylated Akt (p-Akt), cleaved caspase-9 (c-cas9), and cleaved caspase-3 (c-cas3) increased after the reperfusion in the penumbra in vehicle group with peaks at 3 h, 8 h, and 1 day, respectively. Topical application of GDNF (6.8 mug/9mul) on brain surface potentiated and prolonged p-Akt activation but suppressed activation of the caspases and reduced the number of terminal deoxynucleotidyl transferase-mediated dUDP-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.