Modification of the Cortical Impact Model To Produce Axonal Injury in the Rat Cerebral Cortex

Abstract

Diffuse axonal injury (DAI) is a form of brain injury that is characterized by morphologic changes to axons throughout the brain and brainstem. Previous biomechanical studies have shown that primary axonal dysfunction, ranging from minor electrophysiologic disturbances to immediate axotomy, can be related to the rate and level of axonal deformation. Some existing rodent head injury models display varying degrees of axonal injury in the forebrain and brainstem, but the extent of axonal damage in the forebrain has been limited to the contused hemisphere. This study examined whether opening the dura mater over the contralateral hemisphere could direct mechanical deformation across the sagittal midline and produce levels of strain sufficient to cause a more widespread, bilateral forebrain axonal injury following cortical impact. Intracranial deformation patterns produced by this modified cortical impact technique were examined using surrogate skull-brain models. Modeling results revealed that the presence of a contralateral craniotomy significantly reduced surrogate tissue herniation through the foramen magnum, allowed surrogate tissue movement across the sagittal midline, and resulted in an appreciable increase in the shear strain in the contralateral cortex during the impact. To evaluate the injury pattern produced using this novel technique, rat brains were subjected to rigid indentor impact injury of their left somatosensory motor cortex (1.5 mm indentation, 4.5-4.9 m/sec velocity, and 22 msec dwell time) and examined after a 2-7 day survival period. Neurofilament immunohistochemistry revealed numerous axonal retraction balls in the subcortical white matter and overlying deep cortical layers in the right hemisphere beneath the contralateral craniotomy. Retraction balls were not seen at these positions in normals, sham controls, or animals that received cortical impact without contralateral craniotomy and dural opening. The results from these physical modeling and animal experiments indicate that opening of the contralateral dura mater permits translation of sufficient mechanical deformation across the midline to produce a more widespread pattern of axonal injury in the forebrain, a pattern that is distinct from those produced by existing fluid percussion and cortical impact techniques.

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

“…Direct visualization of grid patterns or embedded markers within a transparent silicone gel also provided direct evidence for the unique patterns of deformations that occur with accelerations imposed in different directions and the influence that different skull/gel boundary conditions and ventricular structures have on intracranial strains, showing that the ventricles can redistribute and, in some regions, reduce the strains appearing within the brain after impact [99][100][101][102]. In some instances, these models have been used to assess the effectiveness of different animal models to recreate the deformation patterns that appear during impact and have led to a redesign of animal models to produce deformation patterns that more closely resemble the strains within the hemispheres during injury [103][104][105]. These same techniques are now extended to blast loading conditions [102][103][104][105][106][107][108][109], where the efforts will yield significant information on the manner that external blast waves transfer to the brain simulant, how these pressures are distributed throughout the surrogate, and how these pressures dissipate over time.…”

“…In some instances, these models have been used to assess the effectiveness of different animal models to recreate the deformation patterns that appear during impact and have led to a redesign of animal models to produce deformation patterns that more closely resemble the strains within the hemispheres during injury [103][104][105]. These same techniques are now extended to blast loading conditions [102][103][104][105][106][107][108][109], where the efforts will yield significant information on the manner that external blast waves transfer to the brain simulant, how these pressures are distributed throughout the surrogate, and how these pressures dissipate over time. Although providing a direct window into the possible response of the brain to any external mechanical loading condition, it is worth noting that the highly elastic material properties of brain tissue surrogates will need to be considered in extending or interpreting these results for the viscoelastic, nonlinear brain tissue.…”

Inhibition of Eukaryotic Initiation Factor 2 Alpha Phosphatase Reduces Tissue Damage and Improves Learning and Memory after Experimental Traumatic Brain Injury

“…It has been shown that the presence of bilateral craniectomies shifts intracranial strain distribution to the contralateral hemisphere and causes increased contralateral axonal damage. 41,42 As such, bilateral Craniectomies were chosen in order to increase the likelihood of contralateral hippocampal damage. Rats received a single impact (2.5-mm deformation) on the right parietal lobe with an impact velocity of 5 m/sec.…”

Computational neurotrauma—design, simulation, and analysis of controlled cortical impact model

“…Among these papers, 122 papers reported the use of a unilateral (single) craniotomy, 17 papers reported bilateral craniotomy use, while 95 papers did not report this information. In one unique study, both unilateral and contralateral craniotomies were studied (Meaney et al 1994). Among the 222 papers in which the impact depth was reported, 12 papers utilized two depth levels and six reported three depth levels.…”