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

• 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.

Nyckelord

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

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