title: Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter.
abstract: OBJECTIVE
  The mechanisms underlying brain injury from intracerebral hemorrhage (ICH) are complex and poorly understood. To comprehensively examine pathophysiological and pathochemical alterations after ICH and to examine the effects of hematoma removal on these processes, we developed a physiologically controlled, reproducible, large-animal model of ICH in pigs (weight, 6 to 8 kg).
  
  
  METHODS
  We produced lobar hematomas by pressure- controlled infusions of 1.7 mL of autologous blood into the right frontal hemispheric white matter over 15 minutes. We froze brains in situ at 1, 3, 5, and 8 hours after hematoma induction and cut coronal sections of hematoma assessment, morphological brain examination, and immunohistochemical and water content determinations.
  
  
  RESULTS
  At 1 hour after blood infusion, "translucent" white matter areas were present directly adjacent to the hematoma. These markedly edematous regions had a greater than 10% increase in water content (>85%) compared with the contralateral white matter (73%), and this increased water content persisted through 8 hours. In addition, these areas were strongly immunoreactive for serum proteins. Intravascular Evans blue dye failed to penetrate into the brain tissue at all time points, demonstrating that this serum protein accumulation and edema development were not due to increased blood-brain barrier permeability.
  
  
  CONCLUSIONS
  Experimental lobar ICH in pigs models a prominent pathological feature of human ICH, ie, early perihematomal edema. Our findings suggest that serum proteins, originating from the hematoma, accumulate in adjacent white matter and result in rapid and prolonged edema after ICH. This interstitial edema likely corresponds to the low densities on CT scans and the hyperintensities on T2-weighted MR images that surround intracerebral hematomas acutely after human ICH.
authors.affiliation: Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Wagner
authors.forename: G
authors.initials: G
authors.lastname: Xi
authors.forename: Y
authors.initials: Y
authors.lastname: Hua
authors.forename: M
authors.initials: M
authors.lastname: Kleinholz
authors.forename: G M
authors.initials: GM
authors.lastname: de Courten-Myers
authors.forename: R E
authors.initials: RE
authors.lastname: Myers
authors.forename: J P
authors.initials: JP
authors.lastname: Broderick
authors.forename: T G
authors.initials: TG
authors.lastname: Brott
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D001812:Blood-Brain Barrier; D001834:Body Water / Q000737:chemistry; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002421:Caudate Nucleus; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004396:Coloring Agents; D004195:Disease Models, Animal; D005070:Evans Blue; D006406:Hematoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007267:Injections; D013552:Swine; D013788:Thalamus
chemical_list: D001798:Blood Proteins; D004396:Coloring Agents; D005070:Evans Blue