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.

Immunohistochemical investigation of caspase-3 in neuronal apoptosis after experimental closed head trauma

“…Our results are in agreement with reports of other workers, which suggest that closed head trauma caused apotosis in the frontal cortex (Stone et al, 2002;Lau et al, 2006;Dressler et al, 2007;Kilbourne et al, 2009;Kim et al, 2010).…”

Viscoelastic Properties of the Rat Brain in the Sagittal Plane: Effects of Anatomical Structure and Age

“…For example, a model of frontal impact in the rat caused different injuries than a dorsal impact model. 23 Tissues with aligned fibrous microstructures such as intervertebral disk 14 and blood vessels 32 often have anisotropic mechanical properties. The microstructure of brain is heterogeneous 3 with highly aligned fibers in some structures, such as the corpus callosum.…”

Repeated mild traumatic brain injury: potential mechanisms of damage

“…The impact results in unrestricted movement of the head and body as the animal readily penetrates the material upon impact and free falls onto a padded cushion below. Various other models have been developed to increase rotational acceleration 75 and employ momentum-exchange principles in a frontal impact model 76,77 through the use of a pendulum striker 78,79 as well as projectiles. 80,81 Mechanical input parameters and subsequent outcomes can be more variable in closed-head models incorporating rotational head movement.…”