Document Detail

Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain.
MedLine Citation:
PMID:  16697939     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Fetal brain injury is associated with chorioamnionitis, which is often present without signs of overt infection or fetal compromise. We aimed to determine if prolonged exposure to intrauterine inflammation caused by intra-amniotic infusion of lipopolysaccharide (LPS) would affect the fetal brain. METHODS: At 80 days of pregnancy ewes bearing singletons had osmotic pumps implanted intra-amniotically to infuse Escherichia coli LPS (055:B5; n = 8) or saline (n = 7) for 28 days. At delivery (110 days), umbilical arterial blood and chorioamnion were assessed for inflammation; cytokine concentrations (interleukin [IL]-6 and IL-8) in amniotic fluid and fetal and maternal plasma were measured. The fetal cerebral hemispheres were examined for gross anatomical changes and the number of activated microglia/macrophages, astrocytes, and oligodendrocytes estimated after immunohistochemical staining. RESULTS: Intra-amniotic administration of LPS caused chorioamnionitis, fetal leucocytosis, and a moderate to extensive infiltration of activated microglia/macrophages in the subcortical white matter in six of eight fetuses; the remaining two fetuses were less affected. Within these focal regions of damage there was an attenuation of astrocytic processes, axonal injury, and a reduction in the number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) immunoreactive oligodendrocytes in areas of extensive focal damage. In control fetuses there was mild (3/7) or no infiltration of activated microglia/macrophages in the subcortical white matter. Overall the infiltration of activated microglia/macrophages in the white matter was significantly greater in LPS-exposed fetuses compared to controls. In regions devoid of injury, the number of oligodendrocytes and astrocytes was not different between groups, nor was there a difference in the volume of cerebral white matter or density of blood vessels within the white matter. Amniotic fluid IL-6 and IL-8, and maternal plasma IL-8 concentrations were significantly increased by LPS infusion. CONCLUSIONS: An increase in inflammatory cells and axonal disruption in the subcortical white matter of the fetal brain can accompany chorioamnionitis induced by intra-amniotic administration of LPS, but cystic lesions do not occur. Thus, the effect on the fetal brain is milder than that reported from animal models of acute fetal/intrauterine infection.
Ilias Nitsos; Sandra M Rees; Jhodie Duncan; Boris W Kramer; Richard Harding; John P Newnham; Timothy J M Moss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Society for Gynecologic Investigation     Volume:  13     ISSN:  1556-7117     ISO Abbreviation:  J. Soc. Gynecol. Investig.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-06-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9433806     Medline TA:  J Soc Gynecol Investig     Country:  United States    
Other Details:
Languages:  eng     Pagination:  239-47     Citation Subset:  IM    
School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia.
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MeSH Terms
Amniotic Fluid / chemistry
Blood Cell Count
Brain / cytology,  drug effects*,  embryology*
Cytokines / analysis
Disease Models, Animal
Lectins / analysis
Lipopolysaccharides / toxicity*
Reg. No./Substance:
0/Cytokines; 0/Lectins; 0/Lipopolysaccharides; 0/lipopolysaccharide, E coli O55-B5

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