New pediatric model of ischemic stroke in infant piglets by photothrombosis - Acute changes in cerebral blood flow, microvasculature, and early histopathology

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.