Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury

Y. Wang, C. F. Chang, M. Morales, Y. H. Chiang, J. Hoffer

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)


Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to have trophic activity on dopaminergic neurons. Recent studies indicate that GDNF can protect the cerebral hemispheres from damage induced by middle cerebral arterial ligation. We found that such neuroprotective effects are mediated through specific GDNF receptor alpha-1 (GFRα1). Animals with a deficiency in GFRα-1 have less GDNF-induced neuroprotection. Ischemia also enhances nitric oxide synthase (NOS) activity, which can be attenuated by GDNF. These data suggest that GDNF can protect against ischemic injury through a GFRα-1/NOS mechanism. We also found that the receptor for GDNF, GFRα1, and its signaling moiety c-Ret were upregulated, starting immediately after ischemia. This upregulation suggests that activation of an endogenous neuroprotective mechanism occurs so that responsiveness of GDNF can be enhanced at very early stages during ischemia.

Original languageEnglish
Pages (from-to)423-437
Number of pages15
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2002
Externally publishedYes


  • Cerebral ischemia
  • GDNF
  • MCA ligation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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