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Protective Effects of Glial Cell Line‐Derived Neurotrophic Factor in Ischemic Brain Injury
Author(s) -
WANG Y.,
CHANG C. F.,
MORALES M.,
CHIANG Y. H.,
HOFFER J.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04086.x
Subject(s) - glial cell line derived neurotrophic factor , neuroprotection , neurotrophic factors , gdnf family of ligands , dopaminergic , pharmacology , neuroscience , medicine , receptor , biology , dopamine
A bstract : 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.