Document Detail

Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger.
MedLine Citation:
PMID:  23149557     Owner:  NLM     Status:  MEDLINE    
Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood-brain barrier (BBB). Our previous studies provided evidence that the BBB Na-K-Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210 minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na-K-Cl cotransporter activity.
Martha E O'Donnell; Yi-Je Chen; Tina I Lam; Kelleen C Taylor; Jeffrey H Walton; Steven E Anderson
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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.     Date:  2012-11-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-01     Completed Date:  2013-03-25     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-34     Citation Subset:  IM    
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MeSH Terms
Administration, Intravenous
Anti-Arrhythmia Agents / pharmacology*
Blood-Brain Barrier / metabolism,  pathology
Brain Edema / drug therapy*,  metabolism,  pathology
Brain Infarction / drug therapy,  metabolism,  pathology
Disease Models, Animal
Guanidines / pharmacology*
Infarction, Middle Cerebral Artery
Magnetic Resonance Spectroscopy
Nerve Tissue Proteins / metabolism*
Rats, Sprague-Dawley
Sodium / metabolism*
Sodium-Hydrogen Antiporter / metabolism*
Stroke / drug therapy*,  metabolism
Sulfones / pharmacology*
Grant Support
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Guanidines; 0/Nerve Tissue Proteins; 0/Sodium-Hydrogen Antiporter; 0/Sulfones; 7E3392891K/cariporide; 9NEZ333N27/Sodium

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