Document Detail

Sulfonylurea receptor 1 in the germinal matrix of premature infants.
MedLine Citation:
PMID:  18679166     Owner:  NLM     Status:  MEDLINE    
Germinal matrix (GM) hemorrhage (GMH) is a major cause of mortality and of life-long morbidity from cerebral palsy. GMH is typically preceded by hypoxic/ischemic events and is believed to arise from rupture of weakened veins in the GM. In the CNS, hypoxia/ischemia up-regulate sulfonylurea receptor 1 (SUR1)-regulated NCCa-ATP channels in microvascular endothelium, with channel activation by depletion of ATP being responsible for progressive secondary hemorrhage. We hypothesized that this channel might be up-regulated in the GM of preterm infants at risk for GMH. Here, we studied expression of the regulatory subunit of the channel, SUR1, and its transcriptional antecedent, hypoxia inducible factor 1 (HIF1), in postmortem tissues of premature infants who either were at risk for or who sustained GMH. We found regionally specific up-regulation of HIF1 and of SUR1 protein and mRNA in GM tissues, compared with remote cortical tissues. Up-regulation was prominent in most progenitor cells, whereas in veins, SUR1 was found predominantly in infants who had sustained GMH compared with those without hemorrhage. Our data suggest that the SUR1-regulated NCCa-ATP channel may be associated with GMH, and that pharmacological block of these channels could potentially reduce the incidence of this devastating complication of prematurity.
J Marc Simard; Rudolph J Castellani; Svetlana Ivanova; Michael T Koltz; Volodymyr Gerzanich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Pediatric research     Volume:  64     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-02     Completed Date:  2009-01-22     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  648-52     Citation Subset:  IM    
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MeSH Terms
ATP-Binding Cassette Transporters / genetics,  metabolism*
Brain / blood supply,  metabolism,  pathology
Cerebral Hemorrhage / complications,  mortality,  pathology,  physiopathology*
Cerebral Palsy / etiology,  pathology
Hypoxia-Inducible Factor 1 / genetics,  metabolism*
Infant, Newborn
Infant, Premature*
Potassium Channels, Inwardly Rectifying / genetics,  metabolism*
Premature Birth
Receptors, Drug / genetics,  metabolism*
Sulfonylurea Receptors
Grant Support
Reg. No./Substance:
0/ABCC8 protein, human; 0/Hypoxia-Inducible Factor 1; 0/Potassium Channels, Inwardly Rectifying; 0/Receptors, Drug; 0/Sulfonylurea Receptors

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