title: Novel model of frontal impact closed head injury in the rat.
abstract: 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.
authors.affiliation: Department of Surgery, Walter Reed Army Medical Center , Washington, D.C., USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kilbourne
authors.forename: Reed
authors.initials: R
authors.lastname: Kuehn
authors.forename: Cigdem
authors.initials: C
authors.lastname: Tosun
authors.forename: John
authors.initials: J
authors.lastname: Caridi
authors.forename: Kaspar
authors.initials: K
authors.lastname: Keledjian
authors.forename: Grant
authors.initials: G
authors.lastname: Bochicchio
authors.forename: Thomas
authors.initials: T
authors.lastname: Scalea
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D000054:Acceleration / Q000009:adverse effects; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001696:Biomechanical Phenomena; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D020833:Diffuse Axonal Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005624:Frontal Bone / Q000293:injuries; D016489:Head Injuries, Closed / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010825:Physics; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D012399:Rotation / Q000009:adverse effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D053148:Caspase 3