Time dependent amelioration against ischemic brain damage by glial cell line-derived neurotrophic factor after transient middle cerebral artery occlusion in rat
Wr. Zhang et al., Time dependent amelioration against ischemic brain damage by glial cell line-derived neurotrophic factor after transient middle cerebral artery occlusion in rat, BRAIN RES, 903(1-2), 2001, pp. 253-256
Time dependent influence of glial cell line-derived neurotrophic factor (GD
NF) was examined after 90 min of transient middle cerebral artery occlusion
(MCAO) in rats. Treatment with GDNF significantly reduced the infarct volu
me stained with 2,3,5-triphenyltetrazolium chloride (TTC) when GDNF was top
ically applied at 0 and 1 h of reperfusion, but became insignificant at 3 h
as compared to vehicle group. The protective effect of GDNF was closely re
lated to the significant reduction of the number of terminal deoxynucleotid
yl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) posit
ive cells as well as immunofluorescently positive cells for active forms of
caspases, especially active caspase-3 but not -9. Thus, the present study
showed that topical application of GDNF significantly reduced infarct size
in a time-dependent manner, while the therapeutic time window was shorter t
han other chemical compounds such as an NMDA receptor antagonist (MK-801) a
nd a free radical scavenger (alpha-phenyl-tert-butyl-nitrone, PEN). The eff
ect of GDNF was stronger in suppressing active caspase-3 than active caspas
e-9. (C) 2001 Elsevier Science B.V. All rights reserved.