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Partial loss of VE-cadherin improves long-term outcome and cerebral blood flow after transient brain ischemia in mice
Charite Univ Med Berlin, Klin & Hsch Ambulanz Neurol, Charitepl 1, D-10117 Berlin, Germany.;Charite Univ Med Berlin, Ctr Stroke Res Berlin CSB, Charitepl 1, D-10117 Berlin, Germany..
Charite Univ Med Berlin, Ctr Stroke Res Berlin CSB, Charitepl 1, D-10117 Berlin, Germany.;Charite Univ Med Berlin, Klin & Hsch Ambulanz Psychiat & Psychotherapie, Charite Campus Mitte, Charitepl 1, D-10117 Berlin, Germany..
Charite Univ Med Berlin, Klin & Hsch Ambulanz Neurol, Charitepl 1, D-10117 Berlin, Germany.;Charite Univ Med Berlin, Ctr Stroke Res Berlin CSB, Charitepl 1, D-10117 Berlin, Germany..
Charite Univ Med Berlin, Campus Virchow Klinikum, Klin Neurochirurg, Augustenburger Pl 1, D-13353 Berlin, Germany..
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2016 (English)In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 16, 144Article in journal (Refereed) Published
Abstract [en]

Background: VE-cadherin is the chief constituent of endothelial adherens junctions. However, the role of VE-cadherin in the pathogenesis of cerebrovascular diseases including brain ischemia has not yet been investigated. Methods: VE-cadherin heterozygous (VEC+/-) mice and wildtype controls were subjected to transient brain ischemia by 30 min filamentous middle cerebral artery occlusion (MCAo)/reperfusion. Results: Acute lesion sizes as assessed by MR-imaging on day 3 did not differ between genotypes. Unexpectedly, however, partial loss of VE-cadherin resulted in long-term stroke protection measured histologically on day 28. Equally surprisingly, VEC+/- mice displayed no differences in post-stroke angiogenesis compared to littermate controls, but showed increased absolute regional cerebral blood flow in ischemic striatum at four weeks. The early induction of VE-cadherin mRNA transcription after stroke was reduced in VEC+/- mice. By contrast, N-cadherin and beta-catenin mRNA expression showed a delayed, but sustained, upregulation up to 28 days after MCAo, which was increased in VEC+/ mice. Furthermore, partial loss of VE-cadherin resulted in a pattern of elevated ischemia-triggered mRNA transcription of pericyte-related molecules alpha-smooth muscle actin (alpha-SMA), aminopeptidase N (CD13), and platelet-derived growth factor receptor beta (PDGFR-beta). Conclusions: Partial loss of VE-cadherin results in long term stroke protection. On the cellular and molecular level, this effect appears to be mediated by improved endothelial/pericyte interactions and the resultant increase in cerebral blood flow. Our study reinforces accumulating evidence that long-term stroke outcome depends critically on vascular mechanisms.

Place, publisher, year, edition, pages
2016. Vol. 16, 144
Keyword [en]
Cerebral ischemia, Stroke, Endothelium, Pericyte, Adhesion molecule, Angiogenesis
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-303273DOI: 10.1186/s12883-016-0670-8ISI: 000381825500002PubMedID: 27538712OAI: oai:DiVA.org:uu-303273DiVA: diva2:971357
Funder
German Research Foundation (DFG), SFB TRR43 Exc257EU, European Research Council, 201024 202213 268870
Available from: 2016-09-16 Created: 2016-09-15 Last updated: 2016-09-16Bibliographically approved

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