PMID- 19929375
OWN - NLM
STAT- MEDLINE
DCOM- 20100323
LR  - 20240409
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 26
IP  - 12
DP  - 2009 Dec
TI  - Novel model of frontal impact closed head injury in the rat.
PG  - 2233-43
LID - 10.1089/neu.2009.0968 [doi]
AB  - Frontal impact, closed head trauma is a frequent cause of traumatic brain injury 
      (TBI) in motor vehicle and sports accidents. Diffuse axonal injury (DAI) is 
      common in humans and experimental animals, and results from shearing forces that 
      develop within the anisotropic brain. Because the specific anisotropic properties 
      of the brain are axis-dependent, the anatomical site where force is applied as 
      well as the resultant acceleration, be it linear, rotational, or some 
      combination, are important determinants of the resulting pattern of brain injury. 
      Available rodent models of closed head injury do not reproduce the frontal impact 
      commonly encountered in humans. Here we describe a new rat model of closed head 
      injury that is a modification of the impact-acceleration model of Marmarou. In 
      our model (the Maryland model), the impact force is applied to the anterior part 
      of the cranium and produces TBI by causing anterior-posterior plus sagittal 
      rotational acceleration of the brain inside the intact cranium. Skull fractures, 
      prolonged apnea, and mortality were absent. The animals exhibited petechial 
      hemorrhages, DAI marked by a bead-like pattern of beta-amyloid precursor protein 
      (beta-APP) in damaged axons, and widespread upregulation of beta-APP in neurons, 
      with regions affected including the orbitofrontal cortex (coup), corpus callosum, 
      caudate, putamen, thalamus, cerebellum, and brainstem. Activated caspase-3 was 
      prominent in hippocampal neurons and Purkinje cells at the grey-white matter 
      junction of the cerebellum. Neurobehavioral dysfunction, manifesting as reduced 
      spontaneous exploration, lasted more than 1 week. We conclude that the Maryland 
      model produces diffuse injuries that may be relevant to human brain injury.
FAU - Kilbourne, Michael
AU  - Kilbourne M
AD  - Department of Surgery, Walter Reed Army Medical Center , Washington, D.C., USA.
FAU - Kuehn, Reed
AU  - Kuehn R
FAU - Tosun, Cigdem
AU  - Tosun C
FAU - Caridi, John
AU  - Caridi J
FAU - Keledjian, Kaspar
AU  - Keledjian K
FAU - Bochicchio, Grant
AU  - Bochicchio G
FAU - Scalea, Thomas
AU  - Scalea T
FAU - Gerzanich, Volodymyr
AU  - Gerzanich V
FAU - Simard, J Marc
AU  - Simard JM
LA  - eng
GR  - HL082517/HL/NHLBI NIH HHS/United States
GR  - NS060801/NS/NINDS NIH HHS/United States
GR  - NS061808/NS/NINDS NIH HHS/United States
GR  - NS061934/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Biomarkers)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Acceleration/adverse effects
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Axons/metabolism/pathology
MH  - Biomarkers/analysis/metabolism
MH  - Biomechanical Phenomena
MH  - Brain/*pathology/*physiopathology
MH  - Brain Injuries/metabolism/*pathology/*physiopathology
MH  - Caspase 3/metabolism
MH  - Diffuse Axonal Injury/metabolism/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Frontal Bone/injuries
MH  - Head Injuries, Closed/metabolism/*pathology/*physiopathology
MH  - Hippocampus/metabolism/pathology
MH  - Male
MH  - Neurons/metabolism/pathology
MH  - Physics
MH  - Purkinje Cells/metabolism/pathology
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rotation/adverse effects
PMC - PMC2824220
EDAT- 2009/11/26 06:00
MHDA- 2010/03/24 06:00
PMCR- 2010/12/01
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/03/24 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 10.1089/neu.2009.0968 [pii]
AID - 10.1089/neu.2009.0968 [doi]
PST - ppublish
SO  - J Neurotrauma. 2009 Dec;26(12):2233-43. doi: 10.1089/neu.2009.0968.