title: Delayed inflammatory mRNA and protein expression after spinal cord injury.
abstract: BACKGROUND
  Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation-related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI.
  
  
  METHODS
  Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression.
  
  
  RESULTS
  Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma.
  
  
  CONCLUSIONS
  These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, NW, Washington, DC (20057), USA. kbyrnes@usuhs.mil
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Byrnes
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Washington
authors.forename: Susan M
authors.initials: SM
authors.lastname: Knoblach
authors.forename: Eric
authors.initials: E
authors.lastname: Hoffman
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D000818:Animals; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D046228:Microarray Analysis; D017628:Microglia / Q000502:physiology; D005810:Multigene Family; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D037502:Galectin 3; D011498:Protein Precursors; D012333:RNA, Messenger; D019255:NADPH Oxidases