How does peripheral lipopolysaccharide induce gene expression in the brain of rats?

A. K. Singh, Y. Jiang

Research output: Contribution to journalArticlepeer-review

169 Scopus citations


Lipopolysaccharide (LPS), the principal cell-wall component of gram-negative bacteria, is responsible for alterations in the central and peripheral tissues associated with gram-negative infections. However, the mechanism by which peripheral LPS cause central effects is not fully known. This study showed that peripheral LPS sequentially increased IL-1β and iNOS mRNA levels, NO2 level, and CRF mRNA level in the hypothalamic PVN, and corticosterone concentration in blood. Brain-endothelium, but not hypothalamic PVN samples, from LPS injected rats contained ions for LPS lipids, bound BODIPY-LPS (bLPS), and expressed TLR-4, TLP-2 and CD14 mRNAs. This suggests that (1) LPS does not cross the blood-brain barrier, and (2) brain-endothelial cells contain LPS binding sites, TLR-4, TLR-2 and CD14. Systemic LPS injection increased [14C]sucrose uptake, but did not affect [14C]dextran uptake into the brain. Thus, when injected systemically, LPS binds to its receptor and enter the endothelial cells where it increase BBB permeation in a mass-selective manner and triggers a series of signaling events leading to the development of inflammatory response in the brain.

Original languageEnglish (US)
Pages (from-to)197-207
Number of pages11
Issue number1-3
StatePublished - Sep 1 2004

Bibliographical note

Funding Information:
This project was partially funded by grants from the Graduate School, College of Veterinary Medicine, and Center for Food Safety of the University of Minnesota.

Copyright 2008 Elsevier B.V., All rights reserved.


  • BBB
  • CORT
  • GC
  • GC receptor
  • GR
  • HPP
  • I
  • IL-1β
  • INT
  • LBP
  • blood-brain barrier
  • corticosterone
  • glucocorticoid
  • hypothalamic-pituitary-portal
  • inducible
  • interferon-gamma
  • interleukin-1 beta
  • lipopolysaccharide (LPS) binding protein

Fingerprint Dive into the research topics of 'How does peripheral lipopolysaccharide induce gene expression in the brain of rats?'. Together they form a unique fingerprint.

Cite this