title: Altering leukocyte recruitment following traumatic brain injury with ghrelin therapy.
abstract: BACKGROUND
  Traumatic brain injury (TBI)-induced cerebral inflammation involves several mediators including activation of resident microglia, infiltration of leukocytes, and release of proinflammatory cytokines and chemokines at the site of injury. Invading leukocytes, mainly neutrophil and inflammatory monocytes, contribute to ongoing post-TBI cerebral edema and neuronal injury. Based on the beneficial effect of ghrelin hormone treatment following TBI, we hypothesized that ghrelin may alter the infiltrating inflammatory cell profile.
  
  
  METHODS
  A weight drop model was used to create severe TBI. C57 mice were divided into three groups: sham, no TBI or ghrelin treatment; TBI, TBI only; TBI/ghrelin, animals were treated with ghrelin 20 μg (intraperitoneally) immediately following TBI and again 1 hour later. Seven days after injury, brain sections were immunostained with Iba-1 and CD11b to assess the recruitment and activation of resident microglia and infiltrated leukocytes. Alternatively, brain dissociates were isolated, and flow cytometry was used to gate for microglia (CD11b, CD45 cells), monocytes (CD11b, CD45, F4/80 cells), and neutrophils (CD11b, CD45, F4/80 cells) to measure their recruitment to injury site.
  
  
  RESULTS
  TBI resulted in a rapid invasion (16-fold) of inflammatory leukocytes to the site of injury, which persisted for at least 1 week. Ghrelin treatment significantly reduced infiltration of peripheral leukocytes (2.8-fold). In particular, recruitment of CD11bCD45 inflammatory monocytes (2.4-fold) and CD11bCD45F4/80 neutrophils (1.7-fold) was reduced following ghrelin treatment. There were no observed ghrelin-mediated changes in either the number of CD11bCD45 resident microglia or its activation state.
  
  
  CONCLUSIONS
  Together, our data demonstrate that ghrelin attenuated leukocyte recruitment, which correlates with improved histologic outcome following TBI.
authors.affiliation: From the Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California-San Diego, San Diego, California.
authors.forename: Jisook
authors.initials: J
authors.lastname: Lee
authors.forename: Todd W
authors.initials: TW
authors.lastname: Costantini
authors.forename: Ryan
authors.initials: R
authors.lastname: D'Mello
authors.forename: Brian P
authors.initials: BP
authors.lastname: Eliceiri
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal