Linked Life Data

16680679

Source:http://linkedlifedata.com/resource/pubmed/id/16680679

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-29
pubmed:abstractText
Measurement of oxygen concentration and distribution in the brain is essential for understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that potentially can be used to map O(2) concentration in the brain. We examined two nitroxides, 3-methoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [2] and 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [3], as pro-imaging agents to deliver 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [1] across the blood-brain barrier (BBB). In primary cultured neurons, nitroxide [3] but not [2] was hydrolyzed by intracellular esterases to [1], which, being anionic at physiologic pH, was well retained intracellularly. In contrast, [2] was not well retained by neurons. In vivo pharmacokinetic and pharmacodynamic studies in mice suggested that esterase-labile nitroxide [3] crossed the BBB, and was converted to [1] and retained. Retention occurred in brain tissue and not in the extensive vasculature, as evidenced by the fact that removal of blood by whole-body saline perfusion did not eliminate the nitroxide EPR signal from the brain. The EPR linewidths of [1] and [3] were more O(2)-sensitive than that of the commonly-used oximetry probe 4-oxo-2,2,6,6-tetramethylpiperidine-d(16)-1-(15)N-oxyl [4]. Moreover, we used [3] in vivo to estimate O(2) concentration in mouse brains. These results indicate that nitroxide [3] could be useful for mapping O(2) distribution in the brain following stroke.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0740-3194
pubmed:author
pubmed:copyrightInfo
Copyright 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1433-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Use of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: potential for in vivo measurement of tissue oxygenation in mouse brain.
pubmed:affiliation
Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico, Albuquerque, 87131, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies, Research Support, N.I.H., Extramural