Abstract | BACKGROUND: Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH. Following GMH, iron degraded from hemoglobin has been linked to PHH. Choroid plexus epithelial cells also contain iron-responsive element-binding proteins (IRPs), IRP1, and IRP2 that bind to mRNA iron-responsive elements. The present study aims to resolve the following issues: (1) whether the expression of NCBE is regulated by IRPs; (2) whether NCBE regulates the formation of GMH-induced hydrocephalus; and (3) whether inhibition of NCBE reduces PHH development. METHODS AND RESULTS: CONCLUSIONS: Targeting iron-induced overexpression of NCBE may be a translatable therapeutic strategy for the treatment of PHH following GMH.
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Authors | Qian Li, Yan Ding, Paul Krafft, Weifeng Wan, Feng Yan, Guangyong Wu, Yixin Zhang, Qunling Zhan, John H Zhang |
Journal | Journal of the American Heart Association
(J Am Heart Assoc)
Vol. 7
Issue 3
(01 31 2018)
ISSN: 2047-9980 [Electronic] England |
PMID | 29386206
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. |
Chemical References |
- Chlorides
- Ferric Compounds
- RNA, Small Interfering
- Siderophores
- Sodium-Bicarbonate Symporters
- Iron Regulatory Protein 1
- Iron Regulatory Protein 2
- Deferoxamine
- ferric chloride
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Topics |
- Animals
- Animals, Newborn
- Behavior, Animal
(drug effects)
- Cerebral Hemorrhage
(genetics, metabolism, physiopathology, therapy)
- Cerebrospinal Fluid
(metabolism)
- Chlorides
- Choroid Plexus
(drug effects, metabolism, physiopathology)
- Cognition
(drug effects)
- Deferoxamine
(pharmacology)
- Disease Models, Animal
- Ferric Compounds
- Hydrocephalus
(genetics, metabolism, physiopathology, prevention & control)
- Injections, Intraventricular
- Iron Regulatory Protein 1
(genetics, metabolism)
- Iron Regulatory Protein 2
(genetics, metabolism)
- Motor Activity
(drug effects)
- RNA, Small Interfering
(administration & dosage)
- RNAi Therapeutics
- Rats, Sprague-Dawley
- Siderophores
(pharmacology)
- Sodium-Bicarbonate Symporters
(genetics, metabolism)
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