Article

Neurochemical Research

, Volume 28, Issue 2, pp 215-223

White Matter Injury Following Systemic Endotoxemia or Asphyxia in the Fetal Sheep

  • Carina MallardAffiliated withPerinatal Center, Department of Physiology and Pharmacology, Göteborg University Email author 
  • , Anna-Karin WelinAffiliated withPerinatal Center, Department of Obstetrics and Gynecology, Institute for the Health of Women and Children, Sahlgrenska University Hospital/East
  • , Donald PeeblesAffiliated withDepartment of Obstetrics and Gynecology, University College of London
  • , Henrik HagbergAffiliated withPerinatal Center, Department of Obstetrics and Gynecology, Institute for the Health of Women and Children, Sahlgrenska University Hospital/East
  • , Ingemar KjellmerAffiliated withPerinatal Center, Department of Pediatrics, The Queen Silvia Children's Hospital

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Abstract

White matter injury is the most frequently observed brain lesion in preterm infants. The etiology remains unclear, however, both cerebral hypoperfusion and intrauterine infections have been suggested as risk factors. We compared the neuropathological outcome, including the effect on oligodendrocytes, astrocytes, and microglia, following either systemic asphyxia or endotoxemia in fetal sheep at midgestation. Fetal sheep were subjected to either 25 minutes of umbilical cord occlusion or systemic endotoxemia by administration of Escherichia coli lipopolysaccharide (LPS O111:B4, 100 ng/kg, IV). Periventricular white matter lesions were observed in 2 of 6 asphyxiated fetuses, whereas the remaining animals showed diffuse injury throughout the subcortical white matter and neuronal necrosis in subcortical regions, including the striatum and hippocampus. LPS-treatment resulted in focal inflammatory infiltrates and cystic lesions in periventricular white matter in 2 of 5 animals, but with no neuron specific injury. Both experimental paradigms resulted in microglia activation in the white matter, damaged astrocytes, and loss of oligodendrocytes. These results show that the white matter at midgestation is sensitive to injury following both systemic asphyxia and endotoxemia. Asphyxia induced lesions in both white and subcortical grey matter in association with microglia activation, and endotoxemia resulted in selective white matter damage and inflammation.

Asphyxia periventricular leukomalacia endotoxemia oligodendrocyte infection