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Type: Journal article
Title: Elevated intracranial pressure and cerebral edema following permanent MCA occlusion in an ovine model
Author: Wells, A.
Vink, R.
Helps, S.
Knox, S.
Blumbergs, P.
Turner, R.
Citation: PLoS One, 2015; 10(6):e0130512-1-e0130512-20
Publisher: Public Library of Science
Issue Date: 2015
ISSN: 1932-6203
Statement of
Adam J. Wells, Robert Vink, Stephen C. Helps, Steven J. Knox, Peter C. Blumbergs, Renée J. Turner
Abstract: INTRODUCTION: Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model. MATERIALS AND METHODS: 30 adult female Merino sheep (n = 8-12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed. RESULTS: No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%. CONCLUSIONS: Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies.
Keywords: Brain; Animals; Sheep, Domestic; Brain Edema; Infarction, Middle Cerebral Artery; Intracranial Hypertension; Disease Models, Animal; Oxygen; Tetrazolium Salts; Magnetic Resonance Imaging; Random Allocation; Female; Stroke
Rights: © 2015 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
RMID: 0030032223
DOI: 10.1371/journal.pone.0130512
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