This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 38/6/1932    most recent STROKEAHA.106.475244v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kuluz, J. W. Articles by Watson, B. Search for Related Content PubMed PubMed Citation Articles by Kuluz, J. W. Articles by Watson, B. Pubmed/NCBI databases Medline Plus Health Information Stroke Related Collections Animal models of human disease Arterial thrombosis Acute Cerebral Infarction Embolic stroke

(Stroke. 2007;38:1932.)
© 2007 American Heart Association, Inc.

Original Contributions

New Pediatric Model of Ischemic Stroke in Infant Piglets by Photothrombosis

Acute Changes in Cerebral Blood Flow, Microvasculature, and Early Histopathology

John W. Kuluz, MD; Ricardo Prado, MD; Dansha He, MD; Weizhao Zhao, PhD; W. Dalton Dietrich, PhD Brant Watson, PhD

From the Departments of Pediatrics (J.W.K., D.H.), Neurology (Cerebral Vascular Disease Research Center) (R.P., W.Z., B.W.), and Biomedical Engineering (B.W.), and the Miami Project to Cure Paralysis (W.D.D.), University of Miami Miller School of Medicine, Miami, Fla.

Correspondence to John W. Kuluz, M.D., Associate Professor, Pediatric Critical Care Medicine (R-131), University of Miami School of Medicine, Post Office Box 016960, Miami, Florida E-mail jkuluz{at}med.miami.edu

Background and Purpose— 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.

Key Words: focal ischemia • neuroinflammation • apoptosis • photothrombosis • middle cerebral artery