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 journalArticle

84 Citations (Scopus)

Abstract

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
Volume962
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Brain Injuries
Brain
Glial Cell Line-Derived Neurotrophic Factor Receptors
Ischemia
Nitric Oxide Synthase
Nerve Growth Factor Receptors
Transforming Growth Factors
Neuroprotective Agents
Dopaminergic Neurons
Cerebrum
Neurons
Brain Injury
Cells
Animals
Ligation
Chemical activation
Up-Regulation
Wounds and Injuries

Keywords

  • Cerebral ischemia
  • GDNF
  • MCA ligation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury. / Wang, Y.; Chang, C. F.; Morales, M.; Chiang, Y. H.; Hoffer, J.

In: Annals of the New York Academy of Sciences, Vol. 962, 2002, p. 423-437.

Research output: Contribution to journalArticle

@article{e99ee74328ef4491bf691bf677cdd651,
title = "Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury",
abstract = "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.",
keywords = "Cerebral ischemia, GDNF, MCA ligation",
author = "Y. Wang and Chang, {C. F.} and M. Morales and Chiang, {Y. H.} and J. Hoffer",
year = "2002",
language = "English",
volume = "962",
pages = "423--437",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Protective effects of glial cell line-derived neurotrophic factor in ischemic brain injury

AU - Wang, Y.

AU - Chang, C. F.

AU - Morales, M.

AU - Chiang, Y. H.

AU - Hoffer, J.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Cerebral ischemia

KW - GDNF

KW - MCA ligation

UR - http://www.scopus.com/inward/record.url?scp=0036275026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036275026&partnerID=8YFLogxK

M3 - Article

VL - 962

SP - 423

EP - 437

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -