Beyond white matter damage: fetal neuronal injury in a mouse model of preterm birth.
OBJECTIVE
The purpose of this study was to elucidate possible mechanisms of fetal neuronal injury in inflammation-induced preterm birth.


METHODS
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.


CONCLUSIONS
Lipopolysaccharide-induced preterm birth may be responsible for irreversible neuronal injury.
Burd
Irina
I
Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6142, USA. irina.burd@uphs.upenn.edu
Chai
Jinghua
J
Gonzalez
Juan
J
Ofori
Ella
E
Monnerie
Hubert
H
Le Roux
Peter D
PD
Elovitz
Michal A
MA
D000818:Animals; D001921:Brain / Q000196:embryology*; D020208:Brain Injury, Chronic / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D018920:Coculture Techniques; D005333:Fetus / Q000166:cytology*; D008070:Lipopolysaccharides; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons; D016133:Polymerase Chain Reaction / Q000379:methods; D047928:Premature Birth / Q000473:pathology*
D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D020169:Caspases