Post-injury conditioning with lipopolysaccharide or lipooligosaccharide reduces inflammation in the brain

J Neuroimmunol. 2013 Mar 15;256(1-2):28-37. doi: 10.1016/j.jneuroim.2012.12.009. Epub 2013 Jan 17.

Abstract

Background: Traumatic brain injury (TBI) is a leading cause of mortality and disability in the Western world. The first stage of TBI results from the mechanical damage from an impact or blast. A second stage occurs as an inflammatory response to the primary injury and presents an opportunity for clinical intervention. In this study, we investigated the effect of pre- and post-injury treatment with lipopolysaccharide (LPS) from Escherichia coli and lipooligosaccharide (LOS) from Neisseria meningitidis on levels of cerebral inflammatory cells, circulating blood cells, and pro- and anti-inflammatory cytokine levels in a rat model of neuroinflammation induced by intrastriatal injection of IL-1β to mimic the second stage of TBI.

Methods: LPS or LOS was administered intravenously (IV) or intranasally (IN) 2h pre- or post-injection of IL-1β. The rats were euthanized 12h following IL-1β injection. Brain sections were immunostained with antibody to ED-1, a microglia cell marker. Cells in whole blood were assessed with a VetScan HM2 analyzer, and cytokine levels in sera were analyzed with a Bio-Plex system.

Results: Pre- and post-injury IV administration of LPS or LOS significantly reduced microglia in the brain, and IN pre-treatment with LPS or LOS showed a statistical trend towards reducing microglia. Pre- and post-treatment IV with LOS increased circulating levels of IL-2 and IL-4, whereas IN post-treatment with LPS reduced levels of the inflammatory cytokines, TNF-α and IFN-γ.

Conclusions: The findings strongly support continued investigation of post-conditioning with LPS or LOS as potential neuroprotective treatments for neuroinflammation from TBI.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Blood Cell Count
  • Brain Injuries / complications*
  • Cell Death / drug effects
  • Cytokines / blood
  • Disease Models, Animal
  • Drug Administration Schedule
  • Ectodysplasins / metabolism
  • Encephalitis / etiology*
  • Encephalitis / pathology
  • Encephalitis / prevention & control*
  • Hematocrit
  • Interleukin-1beta / toxicity
  • Lipopolysaccharides / administration & dosage*
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • Monocytes / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Ectodysplasins
  • Interleukin-1beta
  • Lipopolysaccharides
  • lipid-linked oligosaccharides