The influence of immaturity on hypoxic-ischemic brain damage in the rat

Authors

  • John E. Rice III, BS,

    1. Department of Pediatrics (Pediatric Neurology), The Milton S. Hershey Medical Center of The Pennsylvania State University, Hershey, PA 17033
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  • Dr. Robert C. Vannucci MD,

    Corresponding author
    1. Department of Pediatrics (Pediatric Neurology), The Milton S. Hershey Medical Center of The Pennsylvania State University, Hershey, PA 17033
    • Department of Pediatrics (Pediatric Neurology), The Milton S. Hershey Medical Center of The Pennsylvania State University, Hershey, PA 17033
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  • James B. Brierley MD

    1. The Medical Research Council Laboratories. Woodmansterne Rd. Carshalton. Surrev. SM5 4EF. England
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Abstract

Brain damage in the Levine preparation (unilateral common carotid artery ligation with hypoxia) consists of ischemic neuronal alterations in the ipsilateral forebrain. As the model has been restricted to adult animals, unilateral common carotid artery ligation was carried out in 7-day-postnatal rats. Four to 8 hours later the 25 pups were exposed to 8% oxygen at 37°C for 3.5 hours. Controls consisted of littermates subjected to carotid ligation without subsequent hypoxia, hypoxia without prior ligation, and neither ligation nor hypoxia. After hypoxia the animals were returned to their dams and appeared normal for up to 50 hours. All pups were then killed by perfusion-fixation.

Moderate to severe ischemic neuronal changes were seen in the ipsilateral cerebral cortex, striatum, and hippocampus in at least 90% of the animals and included infarction in 56% of the brains. Cortical damage was occasionally laminar but more often occurred in columns at right angles to the pial surface. Unlike adult animals, there was necrosis of white matter, greater ipsilaterally, originating in and spreading from myelinogenic foci. The evolution of ischemic cell change and the associated gliomesodermal reaction was more rapid than in the adult. In 22 additional pups subjected to carotid artery ligation and hypoxia, brains were analyzed for water content. Significant increases (0.6 to 3.3%) in water content of the ipsilateral hemispheres occurred in 11 of 22 brains (50%).

Unilateral ischemia combined with hypoxia in developing rats therefore results in neuronal destruction in the same brain regions as in adult animals, but also causes necrosis of white matter. The incidence of increased water content was similar to that of overt infarction. Thus, as previously shown in the adult, brain edema is a consequence rather than a cause of major ischemic damage in the immature animal.

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