title: Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Wells
authors.affiliation: Faculty of Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.affiliation: Adelaide Centre for Neuroscience Research, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Helps
authors.affiliation: Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Knox
authors.affiliation: Tissue Pathology, South Australia Pathology, Adelaide, South, Australia, 5000, Australia.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Blumbergs
authors.affiliation: Adelaide Centre for Neuroscience Research, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors.forename: Renée J
authors.initials: RJ
authors.lastname: Turner
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D019586:Intracranial Hypertension / Q000209:etiology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D011897:Random Allocation; D034561:Sheep, Domestic; D020521:Stroke / Q000503:physiopathology*; D013778:Tetrazolium Salts / Q000737:chemistry
chemical_list: D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D010100:Oxygen