title: Post-injury conditioning with lipopolysaccharide or lipooligosaccharide reduces inflammation in the brain.
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.
authors: Center for Immunochemistry, 4150 Clement Street, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
authors: Deborah
authors: D
authors: Bingham
authors: Constance M
authors: CM
authors: John
authors: Jack
authors: J
authors: Levin
authors: S Scott
authors: SS
authors: Panter
authors: Gary A
authors: GA
authors: Jarvis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001772:Blood Cell Count; D001930:Brain Injuries / Q000150:complications*; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D053331:Ectodysplasins / Q000378:metabolism; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D006400:Hematocrit; D053583:Interleukin-1beta / Q000633:toxicity; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009000:Monocytes / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053331:Ectodysplasins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides