title: Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke.
abstract: 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.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Little
authors.affiliation: Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.|Department of Radiology, Capio St Göran's Hospital, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Kvist
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Grankvist
authors.affiliation: Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jonsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Karolinska Experimental Research and Imaging Center (KERIC), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Damberg
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Söderman
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Fabian
authors.initials: F
authors.lastname: Arnberg
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Holmin
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002560:Cerebrovascular Circulation; D003097:Collateral Circulation; D004195:Disease Models, Animal; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D020521:Stroke / Q000000981:diagnostic imaging* / Q000473:pathology*