Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth
Presented orally at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, Jan. 26-31, 2009.
Received 27 February 2009; received in revised form 26 April 2009; accepted 1 June 2009.
Objective
The purpose of this study was to elucidate possible mechanisms of fetal neuronal injury in inflammation-induced preterm birth.
Study Design
With the use of a mouse model of preterm birth, the following primary cultures were prepared from fetal brains: (1) control neurons (CNs), (2) lipopolysaccharide-exposed neurons (LNs), (3) control coculture (CCC) that consisted of neurons and glia, and (4) lipopolysaccharide-exposed coculture (LCC) that consisted of lipopolysaccharide-exposed neurons and glia. CNs and LNs were treated with culture media from CN, LN, CCC, and LCC after 24 hours in vitro. Immunocytochemistry was performed for culture characterization and neuronal morphologic evidence. Quantitative polymerase chain reaction was performed for neuronal differentiation marker, microtubule-associated protein 2, and for cell death mediators, caspases 1, 3, and 9.
Results
Lipopolysaccharide exposure in vivo did not influence neuronal or glial content in cocultures but decreased the expression of microtubule-associated protein 2 in LNs. Media from LNs and LCCs induced morphologic changes in control neurons that were comparable with LNs. The neuronal damage caused by in vivo exposure (LNs) could not be reversed by media from control groups.
Conclusion
Lipopolysaccharide-induced preterm birth may be responsible for irreversible neuronal injury.
aMaternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA
bDepartment of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA
Reprints: Irina D. Burd, MD, PhD, Department of Obstetrics and Gynecology, Maternal and Child Health Research Program, Center for Research on Reproduction and Women's Health, University of Pennsylvania, 1353 Biomedical Research Bldg II/III, 421 Curie Blvd, Philadelphia, PA 19104-6142
This project was supported by National Institutes of Health Grant 5-R01-HD046544-0 (M.A.E.) and supported in part by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania. The project described was supported by Grant UL1RR024134 from the National Center for Research Resources.
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Cite this article as: Burd I, Chai J, Gonzalez J, et al. Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth. Am J Obstet Gynecol 2009;201:279.e1-8.
ABSTRACT
Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth