Time dependent amelioration against ischemic brain damage by glial cell line-derived neurotrophic factor after transient middle cerebral artery occlusion in rat

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.