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




Partial loss of VE-cadherin improves long-term outcome and cerebral blood flow after transient brain ischemia in mice - Download this document for free, or read online. Document in PDF available to download.

BMC Neurology

, 16:144

Cerebrovascular disease and stroke

Abstract

BackgroundVE-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.

MethodsVE-cadherin heterozygous VEC mice and wildtype controls were subjected to transient brain ischemia by 30 min filamentous middle cerebral artery occlusion MCAo-reperfusion.

ResultsAcute 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.

ConclusionsPartial 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.

KeywordsCerebral ischemia Stroke Endothelium Pericyte Adhesion molecule Angiogenesis AbbreviationsCBFCerebral blood flow

CD13Aminopeptidase N

MCAoMiddle cerebral artery occlusion

PDGFR-βPlatelet-derived growth factor receptor β

VECVE-cadherin heterozygous

α-SMAα-smooth muscle actin.

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Author: Karen Gertz - Golo Kronenberg - Ria Uhlemann - Vincent Prinz - Ruben Marquina - Monica Corada - Elisabetta Dejana - Matthia

Source: https://link.springer.com/



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