title: A murine model of mild traumatic brain injury exhibiting cognitive and motor deficits.
abstract: BACKGROUND
  Mild traumatic brain injury (TBI) is a serious public health concern affecting more than 1.7 million people in the United States annually. Mild TBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition.
  
  
  METHODS
  We subjected mice to a mild TBI (mTBI-1 or mTBI-2) induced by a weight drop model. We assessed brain injury histologically and biochemically, the latter by serum neuron-specific enolase and glial fibrillary acidic protein. Systemic and brain inflammation were measured by cytokine array. We determined blood-brain barrier integrity by cerebral vascular leakage of micromolecular and macromolecular fluorescent molecules. We evaluated mice using a rotarod device and novel object recognition to measure motor coordination and cognition, respectively.
  
  
  RESULTS
  Mice undergoing mTBI-1 or mTBI-2 had significant deficits in motor coordination and cognition for several days after injury compared with controls. Furthermore, both mTBI-1 and mTBI-2 caused micromolecular leakage in the blood-brain barrier, whereas only mTBI-2 caused macromolecular leakage. Serum neuron-specific enolase and glial fibrillary acidic protein were elevated acutely and corresponded to the degree of injury, but returned to baseline within 24 h. Serum cytokines interleukin-6 and keratinocyte-derived chemokine were significantly increased within 90 min of TBI. Interleukin-6 levels correlated with the degree of injury.
  
  
  CONCLUSIONS
  The current study provides a reproducible model of mild TBI in mice that exhibits pathologic features of mild TBI in humans. Furthermore, our data suggest that serum cytokines, such as IL-6, may be effective biomarkers for severity of head injury.
authors.affiliation: Institute for Military Medicine, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Sung H
authors.initials: SH
authors.lastname: Yang
authors.forename: Josh
authors.initials: J
authors.lastname: Gustafson
authors.forename: Matt
authors.initials: M
authors.lastname: Gangidine
authors.forename: David
authors.initials: D
authors.lastname: Stepien
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schuster
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
authors.forename: Michael D
authors.initials: MD
authors.lastname: Goodman
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001930:Brain Injuries / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019957:Motor Skills Disorders / Q000503:physiopathology*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011597:Psychomotor Performance / Q000502:physiology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D010751:Phosphopyruvate Hydratase
keywords: Chemokines; Combat casualty care; Cytokines; Inflammation; TBI; Trauma