title: In vivo leukocyte-mediated brain microcirculatory inflammation: a comparison of osmotherapies and progesterone in severe traumatic brain injury.
abstract: BACKGROUND
  Mannitol, hypertonic saline, and progesterone may blunt leukocyte recruitment after traumatic brain injury (TBI). We hypothesized that progesterone reduces pericontusional recruitment of leukocytes to a greater extent than either osmotherapy a day after TBI.
  
  
  METHODS
  CD1 mice underwent controlled cortical impact and were treated with osmotherapy (mannitol and hypertonic saline) or progesterone. Thirty-two hours after TBI, live pial microscopy was used to evaluate leukocyte-endothelial interactions and immunohistochemistry was used for the detection of pericontusional tissue polymorphonuclear neutrophils. Neurologic recovery was assessed before sacrifice.
  
  
  RESULTS
  Mannitol resulted in the lowest in vivo leukocyte recruitment compared with progesterone (795 ± 282 vs 1,636 ± 434 LEU/100 μm/minutes, P < .05). Mannitol also displayed lower tissue accumulation of leukocytes as compared with progesterone (5.7 ± 1.7 vs 15.2 ± .1 LEU/mm(2), P = .03). However, progesterone resulted in better neurologic recovery than either osmotherapy.
  
  
  CONCLUSIONS
  Leukocyte recruitment to injured brain is lowest with mannitol administration. How different agents alter progression of secondary brain injury will require further evaluation in humans.
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kumasaka
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Marks
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Eisenstadt
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Murcy
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Davoud
authors.initials: D
authors.lastname: Samadi
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Johnson
authors.affiliation: Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Browne
authors.affiliation: Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: C William
authors.initials: CW
authors.lastname: Schwab
authors.affiliation: Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: jose.pascual@uphs.upenn.edu.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Pascual
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
chemical_list: D012462:Saline Solution, Hypertonic; D008353:Mannitol; D011374:Progesterone
keywords: Intravital microscopy; Neuroinflammation; Osmotherapy; Polymorphonuclear neutrophil; Progesterone; Traumatic brain injury