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Fetal brain injury in experimental intrauterine asphyxia and inflammation in Gottingen minipigs

Journal article
Authors Kristin Lyng
Berit H. Munkeby
David Scheie
Carina Mallard
Henrik Hagberg
Babill Stray-Pedersen
Ola Didrik Saugstad
J. Frederik Froen
Published in J Perinat Med
Volume 34
Issue 3
Pages 226-34
Publication year 2006
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Clinical Sciences
Pages 226-34
Language en
Keywords Animals, Asphyxia/*pathology, Brain/*embryology/*pathology, Disease Models, Animal, Endotoxins/toxicity, Female, Fetal Diseases/*pathology, Fetal Weight, Inflammation/metabolism/*pathology, Microglia/pathology, Necrosis, Neurons/pathology, Pregnancy, Swine, Swine, Miniature, Tumor Necrosis Factor-alpha/metabolism
Subject categories Medical and Health Sciences


OBJECTIVE: To examine fetal brain injury in the Gottingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length. METHODS: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After total asphyxia, brain stem injury was present in the group pretreated with saline (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia activation was more marked in the brain stem (P < 0.05) and posterior white matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this Gottingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.

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