TNF-alpha system response in a rat model of very preterm brain injuries induced by lipopolysaccharide and/or hypoxia-ischemia

Am J Obstet Gynecol. 2009 Nov;201(5):493.e1-10. doi: 10.1016/j.ajog.2009.06.005. Epub 2009 Aug 5.


Objective: The aim of this study was to determine, with the use of a rat model, the expression of tumor necrosis factor (TNF)-alpha, its receptors, and TNF-alpha-converting enzyme in perinatal brain lesions of early premature neonates.

Study design: Lipopolysaccharide (LPS) was injected intraperitoneally in pregnant rats at the end of gestation. At postnatal day 1, the right carotid artery was ligated and followed by exposure to hypoxia. Forebrains (n = 220) were collected to study the TNF-alpha system.

Results: LPS alone or combined with hypoxia-ischemia (HI) led to a slight decrease of intracerebral TNF-alpha, whereas sole HI induced no variation. TNF-alpha-converting enzyme followed the same pattern of expression as TNF-alpha. TNF receptor 1 was up-regulated in forebrains that were submitted to LPS alone or combined with HI. No variation was observed in TNF receptor 2 expression.

Conclusion: The minimal expression of the TNF-alpha system that we observed may indicate that this pathway is not central in the pathogenesis of brain lesions in early premature neonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn*
  • Brain Diseases / metabolism*
  • Brain Ischemia / metabolism
  • Disease Models, Animal*
  • Hypoxia, Brain / metabolism
  • Lipopolysaccharides / administration & dosage
  • Prosencephalon / metabolism*
  • Rats
  • Rats, Inbred Lew
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha