Document Detail


Prodeath or prosurvival: two facets of hypoxia inducible factor-1 in perinatal brain injury.
MedLine Citation:
PMID:  19041643     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia, which occurs in the brain when oxygen availability drops below the normal level, is a major cause of perinatal hypoxic-ischemic injury (HII). The transcriptional factor hypoxia inducible factor-1 (HIF-1) is a key regulator in the pathophysiological response to the stress of hypoxia. Genes regulated by HIF-1 are involved in energy metabolism, erythropoiesis, angiogenesis, vasodilatation, cell survival and apoptosis. Compared with the adult brain, the neonatal brain is different in physiological structure, function, cellular composition and signaling pathway related gene activation and response after hypoxia. The purpose of this review is to determine if developmental susceptibility of the brain after hypoxic/ischemic injury is related to HIF-1alpha, which also plays a pivotal role in the normal brain development. HIF-1alpha regulates both prosurvival and prodeath responses in the neonatal brain and various mechanisms underlie the apparent contradictory effects, including duration of ischemic injury and severity, cell-types, and/or dependent on the nature of the stimulus after HII. Studies report an excessive induction of HIF-1 in the immature brain, which suggests that a cell death promoting role of HIF may prevail. Inhibition of HIF-1alpha and targeted activation of its prosurvival genes appear as a favorable therapeutic strategy. However, a better understanding of multifaceted HIF-1 function during brain development is required to explore potential targets for further therapeutic interventions in the neonate.
Authors:
Wanqiu Chen; Robert P Ostrowski; Andre Obenaus; John H Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2008-11-11
Journal Detail:
Title:  Experimental neurology     Volume:  216     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-16     Completed Date:  2009-03-20     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-15     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Asphyxia Neonatorum / genetics,  metabolism,  physiopathology*
Brain / growth & development*,  metabolism,  physiopathology*
Brain Edema / genetics,  metabolism,  physiopathology
Cell Death / physiology
Cell Survival / physiology
Encephalitis / genetics,  metabolism,  physiopathology
Humans
Hypoxia-Inducible Factor 1 / genetics,  metabolism*
Hypoxia-Ischemia, Brain / genetics,  metabolism,  physiopathology*
Infant, Newborn
Nerve Degeneration / genetics,  metabolism,  physiopathology
Grant Support
ID/Acronym/Agency:
HD43120/HD/NICHD NIH HHS; NS54685/NS/NINDS NIH HHS; R01 HD043120/HD/NICHD NIH HHS; R01 HD043120-05/HD/NICHD NIH HHS; R01 NS054685-03/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1
Comments/Corrections

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