| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Stroke | ||||
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 43 | ||||
| Number of Issue or Book Chapter: | 2 | ||||
| Page Range: | pp. 514-523 | ||||
| Date: | 2012 | ||||
| Institutions: | Medicine > Lehrstuhl für Neurologie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie | ||||
| Identification Number: |
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| Keywords: | CORTICAL SUBARACHNOID HEMORRHAGE; PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; P-GLYCOPROTEIN; A-BETA; MOUSE MODEL; EFFLUX TRANSPORTER; ENDOTHELIAL-CELLS; CLEARANCE; PEPTIDE; amyloid-beta; blood-brain barrier; cerebral amyloid angiopathy; neuroimaging | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 64097 |
Web of ScienceAbstract
Background and Purpose-Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-beta (A beta) deposition in the blood brain barrier (BBB). CAA contributes to injuries of the neurovasculature including lobar hemorrhages, cortical microbleeds, ischemia, and superficial hemosiderosis. We postulate that CAA pathology is partially due to A beta compromising the BBB. ...
Abstract
Background and Purpose-Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-beta (A beta) deposition in the blood brain barrier (BBB). CAA contributes to injuries of the neurovasculature including lobar hemorrhages, cortical microbleeds, ischemia, and superficial hemosiderosis. We postulate that CAA pathology is partially due to A beta compromising the BBB. Methods-We characterized 19 patients with acute stroke with "probable CAA" for neurovascular pathology based on MRI and clinical findings. Also, we studied the effect of A beta on the expression of tight junction proteins and matrix metalloproteases (MMPs) in isolated rat brain microvessels. Results-Two of 19 patients with CAA had asymptomatic BBB leakage and posterior reversible encephalopathic syndrome indicating increased BBB permeability. In addition to white matter changes, diffusion abnormality suggesting lacunar ischemia was found in 4 of 19 patients with CAA; superficial hemosiderosis was observed in 7 of 9 patients. A beta(40) decreased expression of the tight junction proteins claudin-1 and claudin-5 and increased expression of MMP-2 and MMP-9. Analysis of brain microvessels from transgenic mice overexpressing human amyloid precursor protein revealed the same expression pattern for tight junction and MMP proteins. Consistent with reduced tight junction and increased MMP expression and activity, permeability was increased in brain microvessels from human amyloid precursor protein mice compared with microvessels from wild-type controls. Conclusions-Our findings indicate that A beta contributes to changes in brain microvessel tight junction and MMP expression, which compromises BBB integrity. We conclude that A beta causes BBB leakage and that assessing BBB permeability could potentially help characterize CAA progression and be a surrogate marker for treatment response. (Stroke. 2012;43:514-523.)
Metadata last modified: 19 Dec 2024 09:43
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