title: New pediatric model of ischemic stroke in infant piglets by photothrombosis: acute changes in cerebral blood flow, microvasculature, and early histopathology.
abstract: OBJECTIVE
  The etiology and pathophysiology of acute ischemic stroke in children differ greatly from those in adults. The purpose of this study was to establish a new pediatric model of ischemic stroke in infant piglets for use in future studies of the response of the developing brain to focal ischemic injury.
  
  
  METHODS
  Ischemic stroke was produced in male infant piglets (2 to 4 weeks old) by photothrombotic occlusion of the middle cerebral artery. Regional cerebral blood flow was measured with radiolabeled microspheres up to 4 hours after occlusion. Early histopathology, including caspase-3 immunohistochemistry for apoptosis, was examined 4 hours after ischemia. The nature of the thrombus and its interaction with vascular endothelium were assessed by electron microscopy.
  
  
  RESULTS
  Severe ischemia (0 to 15 mL/100 g per min) occurred rapidly in 1.4+/-0.2 g of tissue at 15 minutes and increased to 2.4+/-0.7 g at 4 hours. Similarly, moderate ischemia (16 to 30 mL/100 g per min) was measured in 1.2+/-0.3 g of tissue at 15 minutes and increased to 2.0+/-0.6 g at 4 hours. These regional cerebral blood flow values represent ischemic levels of blood flow in 20% to 25% of the volume of the ischemic hemisphere at 4 hours after ischemia. Ischemic infarction occurred in both gray and white matter, and cerebral microvessels in the ischemic hemisphere contained large numbers of inflammatory leukocytes. Caspase-3-positive cells were few in number and were found in the periphery of the infarct; cell death appeared to occur primarily by necrosis rather than apoptosis at 4 hours. Electron microscopy revealed a pure platelet thrombus firmly attached to the vascular endothelium, which in some areas appeared to be detached from the basement membrane.
  
  
  CONCLUSIONS
  Ischemic stroke can be produced in infant piglets by middle cerebral artery photothrombosis. The stroke involved both gray and white matter and exhibited a robust inflammatory component. The mean infarct volume determined histopathologically amounted to 9.6+/-2.4% of the affected (ipsilateral) hemisphere, which was correlated well with the mass equivalent of tissue (12.0+/-3.5%), in which severe declines in regional cerebral blood flow were observed at 4 hours.
authors.affiliation: Department of Pediatrics, University of Miami School of Medicine, Miami, Florida, USA. jkuluz@med.miami.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Kuluz
authors.forename: Ricardo
authors.initials: R
authors.lastname: Prado
authors.forename: Dansha
authors.initials: D
authors.lastname: He
authors.forename: Weizhao
authors.initials: W
authors.lastname: Zhao
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.forename: Brant
authors.initials: B
authors.lastname: Watson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D008833:Microcirculation / Q000502:physiology; D010777:Photochemistry; D012039:Regional Blood Flow / Q000502:physiology; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology; D013552:Swine; D013927:Thrombosis / Q000473:pathology* / Q000503:physiopathology