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

W. R. Zhang, T. Hayashi, M. Iwai, I. Nagano, K. Sato, Y. Manabe, K. Abe

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)253-256
Number of pages4
JournalBrain Research
Volume903
Issue number1-2
DOIs
Publication statusPublished - Jun 8 2001

Keywords

  • Caspase-3
  • Caspase-9
  • Glial cell line-derived neurotrophic factor (GDNF)
  • Ischemia
  • Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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