| Early brain injury alters the blood-brain barrier phenotype in parallel with β-amyloid and cognitive changes in adulthood. | |
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MedLine Citation:
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PMID: 23149553 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Clinical studies suggest that traumatic brain injury (TBI) hastens cognitive decline and development of neuropathology resembling brain aging. Blood-brain barrier (BBB) disruption following TBI may contribute to the aging process by deregulating substance exchange between the brain and blood. We evaluated the effect of juvenile TBI (jTBI) on these processes by examining long-term alterations of BBB proteins, β-amyloid (Aβ) neuropathology, and cognitive changes. A controlled cortical impact was delivered to the parietal cortex of male rats at postnatal day 17, with behavioral studies and brain tissue evaluation at 60 days post-injury (dpi). Immunoglobulin G extravasation was unchanged, and jTBI animals had higher levels of tight-junction protein claudin 5 versus shams, suggesting the absence of BBB disruption. However, decreased P-glycoprotein (P-gp) on cortical blood vessels indicates modifications of BBB properties. In parallel, we observed higher levels of endogenous rodent Aβ in several brain regions of the jTBI group versus shams. In addition at 60 dpi, jTBI animals displayed systematic search strategies rather than relying on spatial memory during the water maze. Together, these alterations to the BBB phenotype after jTBI may contribute to the accumulation of toxic products, which in turn may induce cognitive differences and ultimately accelerate brain aging. |
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Authors:
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Viorela Pop; Dane W Sorensen; Joel E Kamper; David O Ajao; M Paul Murphy; Elizabeth Head; Richard E Hartman; Jérôme Badaut |
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Publication Detail:
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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:
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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: 33 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-02-01 Completed Date: 2013-03-25 Revised Date: 2013-04-16 |
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: 205-14 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Loma Linda University, Loma Linda, CA 92354, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging* Amyloid beta-Peptides / metabolism* Animals Blood-Brain Barrier / injuries, metabolism*, pathology Brain Injuries / complications, metabolism*, pathology, physiopathology Cerebral Cortex / injuries, metabolism*, pathology, physiopathology Claudin-5 / genetics, metabolism Cognition* Humans Immunoglobulin G / metabolism Male Maze Learning* Rats Rats, Sprague-Dawley Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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R01HD061946/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Claudin-5; 0/Cldn5 protein, rat; 0/Immunoglobulin G |
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