A Modified Controlled Cortical Impact Technique to Model Mild Traumatic Brain Injury Mechanics in Mice

Abstract

For the past 25 years, controlled cortical impact (CCI) has been a useful tool in traumatic brain injury (TBI) research, creating injury patterns that includes primary contusion, neuronal loss, and traumatic axonal damage. However, when CCI was first developed, very little was known on the underlying biomechanics of mild TBI. This paper uses information generated from recent computational models of mild TBI in humans to alter CCI and better reflect the biomechanical conditions of mild TBI. Using a finite element model of CCI in the mouse, we adjusted three primary features of CCI: the speed of the impact to achieve strain rates within the range associated with mild TBI, the shape, and material of the impounder to minimize strain concentrations in the brain, and the impact depth to control the peak deformation that occurred in the cortex and hippocampus. For these modified cortical impact conditions, we observed peak strains and strain rates throughout the brain were significantly reduced and consistent with estimated strains and strain rates observed in human mild TBI. We saw breakdown of the blood–brain barrier but no primary hemorrhage. Moreover, neuronal degeneration, axonal injury, and both astrocytic and microglia reactivity were observed up to 8 days after injury. Significant deficits in rotarod performance appeared early after injury, but we observed no impairment in spatial object recognition or contextual fear conditioning response 5 and 8 days after injury, respectively. Together, these data show that simulating the biomechanical conditions of mild TBI with a modified cortical impact technique produces regions of cellular reactivity and neuronal loss that coincide with only a transient behavioral impairment.

Examining the relationship between blast‐induced mild traumatic brain injury and posttraumatic stress‐related traits

“…The behavior evidence from animal studies appears to indicate that TBI does not produce behaviors strictly analogous to PTSD. In blunt‐force trauma models of mTBI, other studies have failed to show any alteration of fear extinction or spontaneous recovery (Chen et al, ; Sierra‐Mercado et al, ), suggesting that outcomes from neurotrauma do not influence the circuitry involved in the extinguishing of fear. The pattern of effects in mTBI from impact trauma appears to be limited to generalized anxiety.…”

Radiological–pathological correlation of diffusion tensor and magnetization transfer imaging in a closed head traumatic brain injury model

“…23 Examination of MPSR distribution and other mechanical factors (eg von Mises stress and strain) in this TBI model helped ascertain probable injury patterns prior to the injury and improved the accuracy of the radiological-pathological correlation. 32, 57 …”

“…The MPSR were averaged for volumetric mapping as the injury predictor to evaluate the DAI locations in the brain (Fig 2A). 31, 32 …”

Priming the Inflammatory Pump of the CNS after Traumatic Brain Injury

“…These models include midline fluid percussion injury (mFPI) [9] and closed head impact acceleration models [10, 11]. Modifications of these models are used to induce repeated head injuries and mild TBI [12, 13]. Animal models are integral in developing our understanding of the pathophysiology of TBI.…”