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

2003; Taylor & Francis; Volume: 25; Issue: 3 Linguagem: Inglês

10.1179/016164103101201454

1743-1328

Guang Jin, N. Omori, I. Nagano, Yasuhiro Manabe, Mikio Shoji, K. Abe,

Cell death mechanisms and regulation

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 day, respectively. Topical application of GDNF (6.8 µ g/9 µ l) 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 role against ischemic injury by controlling the balance between Akt pathway and caspase cascades.