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BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

Partial loss of VE-cadherin improves long-term outcome and cerebral blood flow after transient brain ischemia in mice

Authors: Karen Gertz, Golo Kronenberg, Ria Uhlemann, Vincent Prinz, Ruben Marquina, Monica Corada, Elisabetta Dejana, Matthias Endres

Published in: BMC Neurology | Issue 1/2016

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Abstract

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 β-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 α-smooth muscle actin (α-SMA), aminopeptidase N (CD13), and platelet-derived growth factor receptor β (PDGFR-β).

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.
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Metadata
Title
Partial loss of VE-cadherin improves long-term outcome and cerebral blood flow after transient brain ischemia in mice
Authors
Karen Gertz
Golo Kronenberg
Ria Uhlemann
Vincent Prinz
Ruben Marquina
Monica Corada
Elisabetta Dejana
Matthias Endres
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0670-8

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