Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/73160
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Type: | Journal article |
Title: | A surgical model of permanent and transient middle cerebral artery stroke in the sheep |
Author: | Wells, A. Vink, R. Blumbergs, P. Brophy, B. Helps, S. Knox, S. Turner, R. |
Citation: | PLoS One, 2012; 7(7):1-9 |
Publisher: | Public Library of Science |
Issue Date: | 2012 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Kleinschnitz, C. |
Statement of Responsibility: | Adam J. Wells, Robert Vink, Peter C. Blumbergs, Brian P. Brophy, Stephen C. Helps, Steven J. Knox and Renée J. Turner |
Abstract: | BACKGROUND: Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA) ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion. MATERIALS AND METHODS: 18 adult male and female Merino sheep were randomly allocated to one of three groups (n = 6/gp): 1) sham surgery; 2) permanent proximal MCA occlusion (MCAO); or 3) temporary MCAO with aneurysm clip. All animals had invasive arterial blood pressure, intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel occlusion or sham surgery animals were killed by perfusion fixation. Brains were processed for histopathological examination and infarct area determination. 6 further animals were randomized to either permanent (n = 3) or temporary MCAO (n = 3) and then had magnetic resonance imaging (MRI) at 4 h after MCAO. RESULTS: Evidence of ischemic injury in an MCA distribution was seen in all stroke animals. The ischemic lesion area was significantly larger after permanent (28.8%) compared with temporary MCAO (14.6%). Sham animals demonstrated no evidence of ischemic injury. There was a significant reduction in brain tissue oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the permanent MCAO animals with a diffusion deficit involving the whole right MCA territory, whereas temporary MCAO animals demonstrated MRA evidence of flow within the right MCA and smaller predominantly cortical diffusion deficits. CONCLUSIONS: Proximal MCAO can be achieved in an ovine model of stroke via a surgical approach. Permanent occlusion creates larger infarct volumes, however aneurysm clip application allows for reperfusion. |
Keywords: | Blood Vessels Animals Sheep Infarction, Middle Cerebral Artery Disease Models, Animal Magnetic Resonance Imaging Time Factors Female Male |
Rights: | Copyright: © 2012 Wells 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. |
DOI: | 10.1371/journal.pone.0042157 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0042157 |
Appears in Collections: | Aurora harvest Medicine publications |
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hdl_73160.pdf | Published version | 434.3 kB | Adobe PDF | View/Open |
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