Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model

Adam J Wells; Robert Vink; Stephen C Helps; Steven J Knox; Peter C Blumbergs; Renée J Turner

doi:10.1371/journal.pone.0130512

Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model

PLoS One. 2015 Jun 29;10(6):e0130512. doi: 10.1371/journal.pone.0130512. eCollection 2015.

Authors

Adam J Wells¹, Robert Vink², Stephen C Helps³, Steven J Knox⁴, Peter C Blumbergs⁵, Renée J Turner³

Affiliations

¹ Adelaide Centre for Neuroscience Research, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia; Department of Neurosurgery, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.
² Faculty of Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
³ Adelaide Centre for Neuroscience Research, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.
⁴ Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.
⁵ Tissue Pathology, South Australia Pathology, Adelaide, South, Australia, 5000, Australia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / pathology*
Brain Edema / etiology
Brain Edema / physiopathology*
Disease Models, Animal
Female
Infarction, Middle Cerebral Artery / physiopathology*
Intracranial Hypertension / etiology
Intracranial Hypertension / physiopathology*
Magnetic Resonance Imaging
Oxygen / analysis
Oxygen / chemistry
Oxygen / metabolism
Random Allocation
Sheep, Domestic
Stroke / physiopathology*
Tetrazolium Salts / chemistry

Substances

Tetrazolium Salts
triphenyltetrazolium
Oxygen

Grants and funding

This study was supported by the National Health and Medical Research Council through Dora Lush Biomedical Postgraduate Fellowship (AJW; 1017721) and the Overseas Biomedical Post-doctoral Training Fellowship (RJT; 519365) and research scholarships from the Neurosurgical Research Foundation (AJW) and Neurosurgical Society of Australasia (AJW). The funding organizations played no role in design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript.