Document Detail

Neonatal mice lacking functional Fas death receptors are resistant to hypoxic-ischemic brain injury.
MedLine Citation:
PMID:  15350969     Owner:  NLM     Status:  MEDLINE    
Neonatal hypoxia-ischemia (HI) upregulates Fas death receptor expression in the brain, and alterations in expression and activity of Fas signaling intermediates occur in neonatal brain injury. B6.MRL-Tnfrsf6(lpr) mice lacking functional Fas death receptors are protected from HI brain damage in cortex, striatum, and thalamus compared to wild-type mice. Expression of Fas death receptor and active caspases increase in the cortex after HI. In wild-type mice, the hippocampus is most severely injured, and the hippocampus is the only region not protected in the B6.MRL-Tnfrsf6(lpr) mice. The selective vulnerability of the hippocampus to injury correlates with (1) lower basal expression of [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory protein (FLIP), (2) increased degradation of spectrin to its 145 or 150 kDa breakdown product, and (3) a higher percentage of non-apoptotic cell death following neonatal HI. We conclude that Fas signaling via both extrinsic and intrinsic caspase cascades causes brain injury following neonatal HI in a region-dependent manner. Basal levels of endogenous decoy proteins may modulate the response to Fas death receptor signaling and provide a novel approach to understanding mechanisms of neonatal brain injury.
Ernest M Graham; R Ann Sheldon; Debra L Flock; Donna M Ferriero; Lee J Martin; Declan P O'Riordan; Frances J Northington
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurobiology of disease     Volume:  17     ISSN:  0969-9961     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-07     Completed Date:  2004-12-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  89-98     Citation Subset:  IM    
Department of Gyn-Ob, Division of Maternal-Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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MeSH Terms
Animals, Newborn / genetics*
Antigens, CD95 / biosynthesis*,  genetics*,  physiology
Brain / metabolism*,  pathology
Hypoxia-Ischemia, Brain / enzymology,  genetics*,  metabolism*,  prevention & control
Mice, Inbred C57BL
Mice, Mutant Strains
Neurons / metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/Antigens, CD95
Erratum In:
Neurobiol Dis. 2005 Jun-Jul;19(1-2):348-9

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