Gene expression dynamics at the neurovascular unit during early regeneration after cerebral ischemia/reperfusion injury in mice

  • With increasing distribution of endovascular stroke therapies, transient middle cerebral artery occlusion (tMCAO) in mice now more than ever depicts a relevant patient population with recanalized M1 occlusion. In this case, the desired therapeutic effect of blood flow restauration is accompanied by breakdown of the blood-brain barrier (BBB) and secondary reperfusion injury. The aim of this study was to elucidate short and intermediate-term transcriptional patterns and the involved pathways covering the different cellular players at the neurovascular unit after transient large vessel occlusion. To achieve this, male C57Bl/6J mice were treated according to an intensive post-stroke care protocol after 60 min occlusion of the middle cerebral artery or sham surgery to allow a high survival rate. After 24 h or 7 days, RNA from microvessel fragments from the ipsilateral and the contralateral hemispheres was isolated and used for mRNA sequencing. Bioinformatic analyses allowed us to depict gene expression changes at two timepoints of neurovascular post-stroke injury and regeneration. We validated our dataset by quantitative real time PCR of BBB-associated targets with well-characterized post-stroke dynamics. Hence, this study provides a well-controlled transcriptome dataset of a translationally relevant mouse model 24 h and 7 days after stroke which might help to discover future therapeutic targets in cerebral ischemia/reperfusion injury.

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Author:Roxane-Isabelle KestnerGND, Franziska Mayser, Rajkumar VutukuriORCiDGND, Lena Hansen, Stefan GüntherORCiD, Robert BrunkhorstGND, Kavi DevrajORCiD, Waltraud PfeilschifterORCiDGND
URN:urn:nbn:de:hebis:30:3-533400
DOI:https://doi.org/10.3389/fnins.2020.00280
Parent Title (English):Frontiers in Neuroscience
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Document Type:Article
Language:English
Date of Publication (online):2020/04/02
Date of first Publication:2020/04/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/04/02
Tag:blood-brain barrier; high-throughput nucleotide sequencing; matrix metalloproteinases; reperfusion injury; stroke; translational medical research
Volume:14
Issue:article 280
Page Number:12
Note:
Copyright © 2020 Kestner, Mayser, Vutukuri, Hansen, Günther, Brunkhorst, Devraj and Pfeilschifter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS-PPN:463780086
Institutes:Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 4.0