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A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice.

Chen Y, Mao H, Yang KH, Abel T, Meaney DF - Front Neurol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Pennsylvania , Philadelphia, PA , USA.

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.

No MeSH data available.


Related in: MedlinePlus

Mild controlled cortical impact induces extravasation of the blood–brain barrier (BBB) at the injured region. The pattern of extravasation is shown and pictorially depicted (A). Co-labeling of EB and Neurotrace® for the cortex (B), CA3 (C), and dentate gyrus (D) show that the EB positive cells are mostly neurons.
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Figure 3: Mild controlled cortical impact induces extravasation of the blood–brain barrier (BBB) at the injured region. The pattern of extravasation is shown and pictorially depicted (A). Co-labeling of EB and Neurotrace® for the cortex (B), CA3 (C), and dentate gyrus (D) show that the EB positive cells are mostly neurons.

Mentions: The modification of the CCI technique produced little to no visible lesion and no visible hemorrhaging immediately after impact, but EB staining appeared throughout the lesion site (Figure 3A). Although some variability in the EB staining intensity occurred across separate animals, there was no difference in the spatial distribution of EB staining. In the cortex, the staining formed an approximate hemispherical pattern. In comparison, a relatively higher concentration of EB staining appeared at the subcortical white matter directly below the impact site. In all animals tested, there was no staining in the cortical region directly contacting the impactor. In the hippocampus, the dorsal CA3 region (stratum pyramidale) and the dentate gyrus (some granular but mainly polymorphic layer) also showed staining. All injured animals had visible staining in the dentate across all five bregma sections analyzed. However, staining in the CA3 was only visible around bregma −1.5 and −2.0. No EB staining was seen in any of the sham animals (Supplemental Figure 1) or on the contralateral side.


A modified controlled cortical impact technique to model mild traumatic brain injury mechanics in mice.

Chen Y, Mao H, Yang KH, Abel T, Meaney DF - Front Neurol (2014)

Mild controlled cortical impact induces extravasation of the blood–brain barrier (BBB) at the injured region. The pattern of extravasation is shown and pictorially depicted (A). Co-labeling of EB and Neurotrace® for the cortex (B), CA3 (C), and dentate gyrus (D) show that the EB positive cells are mostly neurons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061598&req=5

Figure 3: Mild controlled cortical impact induces extravasation of the blood–brain barrier (BBB) at the injured region. The pattern of extravasation is shown and pictorially depicted (A). Co-labeling of EB and Neurotrace® for the cortex (B), CA3 (C), and dentate gyrus (D) show that the EB positive cells are mostly neurons.
Mentions: The modification of the CCI technique produced little to no visible lesion and no visible hemorrhaging immediately after impact, but EB staining appeared throughout the lesion site (Figure 3A). Although some variability in the EB staining intensity occurred across separate animals, there was no difference in the spatial distribution of EB staining. In the cortex, the staining formed an approximate hemispherical pattern. In comparison, a relatively higher concentration of EB staining appeared at the subcortical white matter directly below the impact site. In all animals tested, there was no staining in the cortical region directly contacting the impactor. In the hippocampus, the dorsal CA3 region (stratum pyramidale) and the dentate gyrus (some granular but mainly polymorphic layer) also showed staining. All injured animals had visible staining in the dentate across all five bregma sections analyzed. However, staining in the CA3 was only visible around bregma −1.5 and −2.0. No EB staining was seen in any of the sham animals (Supplemental Figure 1) or on the contralateral side.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Pennsylvania , Philadelphia, PA , USA.

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.

No MeSH data available.


Related in: MedlinePlus