title: Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets.
abstract: BACKGROUND
  The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression.
  
  
  METHODS
  To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury.
  
  
  RESULTS
  Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical slices. Chemokine and PTGS2 mRNAs remained elevated in slices at 24 h, whereas IL-1β and TNF-α expressions decreased from earlier peak levels. At 24 h after cortical injury in 1-month-old piglets, the expression of CCL2 mRNA was significantly increased in the lesion core and in the penumbra region. The expression of PTGS2, IL-1β, and TNF-α was variable among the piglets.
  
  
  CONCLUSIONS
  These in vitro and large animal models of cortical injury expand our understanding of the early timing and spread of the immunological response and can serve as preclinical systems to facilitate the discovery of therapeutic agents for TBI aimed at regulating inflammatory mediator expression.
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH, 03756, USA. David.J.Graber@Dartmouth.Edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Graber
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. BETHCOSTINE@mgh.harvard.edu.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Costine
authors.affiliation: Department of Pathology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH, 03756, USA. William.F.Hickey@Dartmouth.Edu.
authors.forename: William F
authors.initials: WF
authors.lastname: Hickey
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications*; D002540:Cerebral Cortex / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051546:Cyclooxygenase 2