title: Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin.
abstract: OBJECTIVE
  To investigate the effects of recombinant human erythropoietin on brain oxygenation in a model of diffuse traumatic brain injury.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  Neurosciences and physiology laboratories.
  
  
  METHODS
  Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were intravenously administered with either a saline solution or a recombinant human erythropoietin (5000 IU/kg). A third group received no traumatic brain injury insult (sham-operated).
  
  
  RESULTS
  Three series of experiments were conducted 2 hours after traumatic brain injury to investigate: 1) the effect of recombinant human erythropoietin on brain edema using diffusion-weighted magnetic resonance imaging and measurements of apparent diffusion coefficient (n = 11 rats per group); local brain oxygen saturation, mean transit time, and blood volume fraction were subsequently measured using a multiparametric magnetic resonance-based approach to estimate brain oxygenation and brain perfusion in the neocortex and caudoputamen; 2) the effect of recombinant human erythropoietin on brain tissue PO₂ in similar experiments (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 rat per group). Compared with the sham-operated group, traumatic brain injury saline rats showed a significant decrease in local brain oxygen saturation and in brain tissue PO₂ alongside brain edema formation and microvascular lumen collapse at H2. Treatment with recombinant human erythropoietin reversed all of these traumatic brain injury-induced changes. Brain perfusion (mean transit time and blood volume fraction) was comparable between the three groups of animals.
  
  
  CONCLUSIONS
  Our findings indicate that brain hypoxia can be related to microcirculatory derangements and cell edema without evidence of brain ischemia. These changes were reversed with post-traumatic administration of recombinant human erythropoietin, thus offering new perspectives in the use of this drug in brain injury.
authors.affiliation: INSERM, U836, Grenoble, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouzat
authors.forename: Anne
authors.initials: A
authors.lastname: Millet
authors.forename: Yvonnick
authors.initials: Y
authors.lastname: Boue
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet-Gallay
authors.forename: Thibaut
authors.initials: T
authors.lastname: Trouve-Buisson
authors.forename: Lucie
authors.initials: L
authors.lastname: Gaide-Chevronnay
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Payen
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012307:Risk Factors
chemical_list: D004921:Erythropoietin