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Preserved collateral blood flow in the endovascular M2CAO model allows for clinically relevant profiling of injury progression in acute ischemic stroke
KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169541Article in journal (Refereed) Published
Abstract [en]

Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury. © 2017 Little et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Place, publisher, year, edition, pages
Plos , 2017. Vol. 12, no 1, article id e0169541
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Clinical Medicine
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URN: urn:nbn:se:kth:diva-201760DOI: 10.1371/journal.pone.0169541Scopus ID: 2-s2.0-85009070706OAI: oai:DiVA.org:kth-201760DiVA, id: diva2:1075796
Note

Funding text: The study was funded and supported by the Swedish Society of Medicine, Söderbergska Stiftelsen, Uppdrag Besegra Stroke (supported by the Swedish Heart-Lung Foundation, Karolinska Institutet, Friends of Karolinska Institutet US and the Swedish order of St John), Åhlén-stiftelsen, Thurings stiftelse, Tore Nilsons stiftelse. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

QC 20170221

Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-11-29Bibliographically approved

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