Jin G, Omori N, Li F, Nagano I, Manabe Y, Shoji M, Abe K
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Neurol Res. 2003 Apr;25(3):249-53. doi: 10.1179/016164103101201454.
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 micrograms/9 microliters) 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.
