Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability following tissue plasminogen activator related to claudin 5 and occludin disassembly

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DOIResolve DOI: http://doi.org/10.1038/jcbfm.2011.79
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TypeArticle
Journal titleJournal of Cerebral Blood Flow and Metabolism
ISSN0271-678X
Volume31
Issue9
Pages18741885; # of pages: 12
Subjectalteplase; claudin 5; gadolinium pentetate; occludin; age distribution; aged; aging; animal experiment; animal model; article; blood brain barrier; brain hematoma; brain ischemia; controlled study; disease exacerbation; drug megadose; male; middle cerebral artery occlusion; nonhuman; nuclear magnetic resonance imaging; priority journal; protein assembly; protein phosphorylation; rat; reperfusion injury; Age Factors; Aging; Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Male; Membrane Proteins; Permeability; Rats; Rats, Wistar; Tissue Plasminogen Activator
AbstractGreat uncertainty exists as to whether aging enhances the detrimental effects of tissue plasminogen activator (tPA) on vascular integrity of the ischemic brain. We hypothesized that tPA treatment would augment ischemic injury by causing increased blood-brain barrier (BBB) breakdown as determined by quantitative serial T 1 and T 2 magnetic resonance imaging (MRI), and the transfer constant for gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) from blood to brain in aged (18 to 20 months) compared with young (3 to 4 months) Wistar rats after middle cerebral artery occlusion, mediated through the acute disassembly of claudin 5 and occludin. Increased T 2 values over the first hour of postreperfusion were independently augmented following treatment with tPA (P<0.001) and aging (P<0.01), supporting a synergistic effect of tPA on the aged ischemic brain. Blood-brain barrier permeability for Gd-DTPA (K Gd) was substantial following reperfusion in all animal groups and was exacerbated by tPA treatment in the elderly rat (P<0.001). The frequency of hematoma formation was proportionately increased in the elderly ischemic brain (P<0.05). Both tPA and age independently increased claudin 5 and occludin phosphorylation during ischemia. Early BBB permeability detected by quantitative MRI following ischemic stroke is enhanced by increased age and tPA and is related to claudin 5 and occludin phosphorylation. © 2011 ISCBFM All rights reserved.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biodiagnostics (IBD-IBD)
Peer reviewedYes
NPARC number21271111
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Record identifierae12c4a7-5885-474d-9f42-8acdfa74a406
Record created2014-03-24
Record modified2016-05-09
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