title: Ghrelin decreases motor deficits after traumatic brain injury.
abstract: Pharmacologic therapy for traumatic brain injury (TBI) has remained relatively unchanged for decades. Ghrelin, an endogenously produced peptide, has been shown to prevent apoptosis and blood-brain barrier dysfunction after TBI. We hypothesize that ghrelin treatment will prevent neuronal degeneration and improve motor coordination after TBI.
  
  
  
  A weight drop model created severe TBI in three groups of BALB/c mice: Sham, TBI, and TBI + ghrelin (20 μg intraperitoneal ghrelin). Brain tissue was examined by hematoxylin and eosin and Fluoro-Jade B (FJB) staining to evaluate histologic signs of injury, cortical volume loss, and neuronal degeneration. Additionally, motor coordination was assessed.
  
  
  
  Ghrelin treatment prevented volume loss after TBI (19.4 ± 9.8 mm(3)versus 71.4 ± 31.4 mm(3); P < 0.05). Similarly, although TBI increased FJB-positive neuronal degeneration, ghrelin treatment decreased FJB staining in TBI resulting in immunohistologic patterns similar to sham. Compared with sham, TBI animals had a significant increase in foot faults at d 1, 3, and 7 (2.75 ± 0.42; 2.67 ± 0.94; 3.33 ± 0.69 versus 0.0 ± 0.0; 0.17 ± 0.19; 0.0 ± 0.0; P < 0.001). TBI + ghrelin animals had significantly decreased foot faults compared with TBI at d 1, 3, and 7 (0.42 ± 0.63; 0.5 ± 0.43; 1.33 ± 0.58; P versus TBI <0.001; P versus sham = NS).
  
  
  
  Ghrelin treatment prevented post-TBI cortical volume loss and neurodegeneration. Furthermore, ghrelin improved post-TBI motor deficits. The mechanisms of these effects are unclear; however, a combination of the anti-apoptotic and inflammatory modulatory effects of ghrelin may play a role. Further studies delineating the mechanism of these observed effects are warranted.
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Lopez
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Gaston
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Karina R
authors.initials: KR
authors.lastname: Lopez
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Hageny
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: James
authors.initials: J
authors.lastname: Putnam
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Brian
authors.initials: B
authors.lastname: Eliceiri
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA.
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.affiliation: Division of Trauma, Surgical Critical Care and Burns, Department of Surgery, University of California San Diego, San Diego, CA. Electronic address: v3bansal@ucsd.edu.
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019957:Motor Skills Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D054439:Ghrelin
keywords: Ghrelin; Motor outcomes; TBI