| 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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MedLine Citation:
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PMID: 21610723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Great 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. |
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Authors:
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Jaspreet Kaur; Ursula I Tuor; Zonghang Zhao; Philip A Barber |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-25 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-02 Completed Date: 2011-10-27 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1874-85 Citation Subset: IM |
Affiliation:
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Department of Clinical Neurosciences, Experimental Imaging Centre and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Aging Animals Blood-Brain Barrier / drug effects*, metabolism, pathology Brain / drug effects*, metabolism, pathology Brain Ischemia / drug therapy*, metabolism, pathology Fibrinolytic Agents / pharmacology, therapeutic use* Infarction, Middle Cerebral Artery / drug therapy, metabolism, pathology Magnetic Resonance Imaging Male Membrane Proteins / metabolism* Permeability / drug effects Rats Rats, Wistar Tissue Plasminogen Activator / pharmacology, therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Cldn5 protein, rat; 0/Fibrinolytic Agents; 0/Membrane Proteins; 0/occludin; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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