title: Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model.
abstract: BACKGROUND
  Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.
  
  
  METHODS
  Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons.
  
  
  RESULTS
  MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.
  
  
  CONCLUSIONS
  The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Small Animal and Surgery, University of Georgia, Athens, GA 30602, USA.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Platt
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Veterinary Biosciences & Diagnostic Imaging, University of Georgia, Athens, GA 30602, USA.
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Holmes
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Pathology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Howerth
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Kylee Jo J
authors.initials: KJJ
authors.lastname: Duberstein
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: C Robert
authors.initials: CR
authors.lastname: Dove
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Kinder
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Wyatt
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Amie V
authors.initials: AV
authors.lastname: Linville
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Vivian W
authors.initials: VW
authors.lastname: Lau
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Stice
authors.affiliation: Department of Neurology, Georgia Regents University, Augusta, GA 30912, USA.|Department of Cellular Biology & Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Department of Neurology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Hess
authors.affiliation: Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.|Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Franklin D
authors.initials: FD
authors.lastname: West