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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 persists 8 days after mild controlled cortical impact. Eight days after injury, Fluoro-Jade B staining was located in the cortex (ii), dentate gyrus (iv), and thalamus (vi) (A). The contralateral regions did not show similar FJB staining (i, iii, v). (B) Degeneration in the cortex was still significantly elevated at 8 days compared to sham (p < 0.001 for all sections). (C) In the hippocampus, all sections show significant increase in FJB staining (bregma −1.5 p = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). (D) In the thalamus, all sections showed significant levels of FJB staining (−1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). Samples sizes were n = 5 for sham, n = 11 for injured. Data are expressed as media ± SEM.
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Figure 5: Neuronal degeneration persists 8 days after mild controlled cortical impact. Eight days after injury, Fluoro-Jade B staining was located in the cortex (ii), dentate gyrus (iv), and thalamus (vi) (A). The contralateral regions did not show similar FJB staining (i, iii, v). (B) Degeneration in the cortex was still significantly elevated at 8 days compared to sham (p < 0.001 for all sections). (C) In the hippocampus, all sections show significant increase in FJB staining (bregma −1.5 p = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). (D) In the thalamus, all sections showed significant levels of FJB staining (−1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). Samples sizes were n = 5 for sham, n = 11 for injured. Data are expressed as media ± SEM.

Mentions: Neurodegeneration indicated with FJB staining was sustained 8 days post injury, although the staining was reduced relative to 24 h labeling. Although the level of positively stained cells in the cortex was reduced (Figure 5A), the pattern of FJB positive cells was still similar to that seen in at the 24-h time point. The number of FJB positive cells was still significant compared to sham controls (for cortical degeneration, Figures 5Ai,ii,B, p < 0.001 for all sections). Staining persisted in the CA3 and a significant retention of staining in the dentate gyrus appeared at this longer time point compared to sham (Figures 5Aiii,iv,C, bregma −1.5 = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). A new area of significant labeling appeared in the thalamus at this timepoint (Figures 5Av,vi,D, bregma −1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). A Nissl stain revealed no obvious neuronal loss in these regions (data not shown).


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 persists 8 days after mild controlled cortical impact. Eight days after injury, Fluoro-Jade B staining was located in the cortex (ii), dentate gyrus (iv), and thalamus (vi) (A). The contralateral regions did not show similar FJB staining (i, iii, v). (B) Degeneration in the cortex was still significantly elevated at 8 days compared to sham (p < 0.001 for all sections). (C) In the hippocampus, all sections show significant increase in FJB staining (bregma −1.5 p = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). (D) In the thalamus, all sections showed significant levels of FJB staining (−1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). Samples sizes were n = 5 for sham, n = 11 for injured. Data are expressed as media ± SEM.
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Figure 5: Neuronal degeneration persists 8 days after mild controlled cortical impact. Eight days after injury, Fluoro-Jade B staining was located in the cortex (ii), dentate gyrus (iv), and thalamus (vi) (A). The contralateral regions did not show similar FJB staining (i, iii, v). (B) Degeneration in the cortex was still significantly elevated at 8 days compared to sham (p < 0.001 for all sections). (C) In the hippocampus, all sections show significant increase in FJB staining (bregma −1.5 p = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). (D) In the thalamus, all sections showed significant levels of FJB staining (−1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). Samples sizes were n = 5 for sham, n = 11 for injured. Data are expressed as media ± SEM.
Mentions: Neurodegeneration indicated with FJB staining was sustained 8 days post injury, although the staining was reduced relative to 24 h labeling. Although the level of positively stained cells in the cortex was reduced (Figure 5A), the pattern of FJB positive cells was still similar to that seen in at the 24-h time point. The number of FJB positive cells was still significant compared to sham controls (for cortical degeneration, Figures 5Ai,ii,B, p < 0.001 for all sections). Staining persisted in the CA3 and a significant retention of staining in the dentate gyrus appeared at this longer time point compared to sham (Figures 5Aiii,iv,C, bregma −1.5 = 0.0105, −2.0 p = 0.0018, −2.5 p = 0.0102, −3.0 p = 0.0058, −3.5 p = 0.0338). A new area of significant labeling appeared in the thalamus at this timepoint (Figures 5Av,vi,D, bregma −1.5 p = 0.0024, −2.0 and −2.5 p < 0.001, −3.0 p = 0.0081, −3.5 p = 0.0323). A Nissl stain revealed no obvious neuronal loss in these regions (data not shown).

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