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 (GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with GDNF significantly reduced the infarct volume stained with 2,3,5-triphenyltetrazolium chloride (TTC) when GDNF was topically 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 related to the significant reduction of the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) positive 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 than other chemical compounds such as an NMDA receptor antagonist (MK-801) and a free radical scavenger (alpha-phenyl-tert-butyl-nitrone, PBN). The effect of GDNF was stronger in suppressing active caspase-3 than active caspase-9.
Zhang
W R
WR
Department of Neurology, Okayama University Medical School, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Hayashi
T
T
Iwai
M
M
Nagano
I
I
Sato
K
K
Manabe
Y
Y
Abe
K
K
D000818:Animals; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases