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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

Neuronal degeneration appears 24 h following mild controlled cortical impact. Fluoro-Jade B (FJB) positive cells appeared in the cortex (iv), dentate gyrus (v), and CA3 (vi) on the ipsilateral side; no labeling was observed in the contralateral hemisphere [(i–iii), respectively] (A). (B) The number of FJB positive cells in injured animals was significantly increased compared to sham in both the cortical and hippocampal regions for bregma sections −1.5 to −3.0 (cortex p < 0.001 for each section −1.5 to −3.0, for section −3.5 p = 0.0635, hippocampus p = 0.0113 for section −1.5, p < 0.001 for sections −2.0 to −3.5; n = 5 sham, n = 10 injured). Data are expressed as media ± SEM.
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Figure 4: Neuronal degeneration appears 24 h following mild controlled cortical impact. Fluoro-Jade B (FJB) positive cells appeared in the cortex (iv), dentate gyrus (v), and CA3 (vi) on the ipsilateral side; no labeling was observed in the contralateral hemisphere [(i–iii), respectively] (A). (B) The number of FJB positive cells in injured animals was significantly increased compared to sham in both the cortical and hippocampal regions for bregma sections −1.5 to −3.0 (cortex p < 0.001 for each section −1.5 to −3.0, for section −3.5 p = 0.0635, hippocampus p = 0.0113 for section −1.5, p < 0.001 for sections −2.0 to −3.5; n = 5 sham, n = 10 injured). Data are expressed as media ± SEM.

Mentions: One day after injury, FJB staining showed a similar pattern to the EB staining (Figures 4Ai–vi), with a hemispherical degeneration pattern appearing immediately beneath the impact site. The cortical surface in direct contact with the indentor had no FJB staining. There was also elevated FJB staining in the subcortical white matter directly below the impact site. In the hippocampus, there were FJB positive cells in CA3 regions (stratum pyramidale) in bregma sections −1.5 and −2.0 but not in subsequent sections (Figure 4Avi). Staining in the dentate gyrus was apparent in all five bregma sections analyzed with the staining localized more to the polymorphic layer (Figure 4Av). Since FJB has been shown to co-label with astrocytes (78) sections were triple labeled with GFAP, FJB, and a fluorescent Nissl stain to determine which cell type(s) were FJB positive (data not shown). All FJB positive cells were positive for the Nissl stain and not GFAP. There was little to no FJB stained positive cells in the sham and on the contralateral side (Figures 4Ai–iii). In the sections imaged across the lesion, most showed significant levels of FJB positive cells between sham and injured animals (Figure 4B). Sections −1.5 to −3.0 showed significant FJB positive cells for both the cortex and hippocampus (cortex p < 0.001 for each section −1.5 to −3.0; hippocampus p = 0.0113 for section 1.5, p < 0.001 for sections −2.0 to −3.5). For section −3.5, the cortex trended toward significance at p = 0.0635.


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)

Neuronal degeneration appears 24 h following mild controlled cortical impact. Fluoro-Jade B (FJB) positive cells appeared in the cortex (iv), dentate gyrus (v), and CA3 (vi) on the ipsilateral side; no labeling was observed in the contralateral hemisphere [(i–iii), respectively] (A). (B) The number of FJB positive cells in injured animals was significantly increased compared to sham in both the cortical and hippocampal regions for bregma sections −1.5 to −3.0 (cortex p < 0.001 for each section −1.5 to −3.0, for section −3.5 p = 0.0635, hippocampus p = 0.0113 for section −1.5, p < 0.001 for sections −2.0 to −3.5; n = 5 sham, n = 10 injured). Data are expressed as media ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Neuronal degeneration appears 24 h following mild controlled cortical impact. Fluoro-Jade B (FJB) positive cells appeared in the cortex (iv), dentate gyrus (v), and CA3 (vi) on the ipsilateral side; no labeling was observed in the contralateral hemisphere [(i–iii), respectively] (A). (B) The number of FJB positive cells in injured animals was significantly increased compared to sham in both the cortical and hippocampal regions for bregma sections −1.5 to −3.0 (cortex p < 0.001 for each section −1.5 to −3.0, for section −3.5 p = 0.0635, hippocampus p = 0.0113 for section −1.5, p < 0.001 for sections −2.0 to −3.5; n = 5 sham, n = 10 injured). Data are expressed as media ± SEM.
Mentions: One day after injury, FJB staining showed a similar pattern to the EB staining (Figures 4Ai–vi), with a hemispherical degeneration pattern appearing immediately beneath the impact site. The cortical surface in direct contact with the indentor had no FJB staining. There was also elevated FJB staining in the subcortical white matter directly below the impact site. In the hippocampus, there were FJB positive cells in CA3 regions (stratum pyramidale) in bregma sections −1.5 and −2.0 but not in subsequent sections (Figure 4Avi). Staining in the dentate gyrus was apparent in all five bregma sections analyzed with the staining localized more to the polymorphic layer (Figure 4Av). Since FJB has been shown to co-label with astrocytes (78) sections were triple labeled with GFAP, FJB, and a fluorescent Nissl stain to determine which cell type(s) were FJB positive (data not shown). All FJB positive cells were positive for the Nissl stain and not GFAP. There was little to no FJB stained positive cells in the sham and on the contralateral side (Figures 4Ai–iii). In the sections imaged across the lesion, most showed significant levels of FJB positive cells between sham and injured animals (Figure 4B). Sections −1.5 to −3.0 showed significant FJB positive cells for both the cortex and hippocampus (cortex p < 0.001 for each section −1.5 to −3.0; hippocampus p = 0.0113 for section 1.5, p < 0.001 for sections −2.0 to −3.5). For section −3.5, the cortex trended toward significance at p = 0.0635.

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