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Intrauterine Endotoxin Administration Leads to White Matter Diffusivity Changes in Newborn Rabbits

Carman and Ann Adams Department of Pediatrics Wayne State University School of Medicine, Detroit, Michigan

Sujatha Kannan, MD

Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, skannan{at}med.wayne.edu

Malek Makki, PhD

Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan

Otto Muzik, PhD

Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan

James Janisse, PhD

Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan

Roberto Romero, MD

Department of Molecular Medicine and Genetics Wayne State University School of Medicine, Detroit, Michigan, Perinatology Research Branch, Department of Health and Human Services, National Institute of Child Health and Human Development, National Institutes of Health

Diane Chugani, PhD

Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan

Maternal intrauterine inflammation has been implicated in the development of periventricular leukomalacia and white matter injury in the neonate. We hypothesized that intrauterine endotoxin administration would lead to microstructural changes in the neonatal rabbit white matter in vivo that could be detected at birth using diffusion tensor magnetic resonance imaging (MRI). Term newborn rabbit kits (gestational age 31 days) born to dams exposed to saline or endotoxin in utero on gestational day 28 underwent diffusion tensor imaging, and brain sections were stained for microglia. Comparison between normal and endotoxin groups showed significant decreases in both fractional anisotropy and eigenvalue (e₁) in all periventricular white matter regions that showed an increase in the number of activated microglial cells, indicating that after maternal inflammation, microglial infiltration may predominantly explain this change in diffusivity in the immediate neonatal period. Diffusion tensor imaging may be a clinically useful tool for detecting neuroinflammation induced by maternal infection in neonatal white matter.

Key Words: periventricular leukomalacia • cerebral palsy • neuroinflammation • diffusion tensor imaging • fractional anisotropy • intrauterine inflammation • microglia • New Zealand white rabbits

Journal of Child Neurology, Vol. 24, No. 9, 1179-1189 (2009)
DOI: 10.1177/0883073809338213


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